Summary
In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, γ-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than the one messenger molecule. The exact functional role of such coesisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more compex than perhaps hitherto assumed.
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Agid, Y., Javoy, F., and Glowinski, J., Hyperactivity of remaining dopaminergic neurones after partial destruction of the nigro-striatal dopaminergic system in the rat. Nature New Biol.245 (1973) 150–151.
Allen, J.M., Tatemoto, K., Polak, J.M., Hughes, J., and Bloom, S.R., Two novel related peptides, neuropeptide Y (NPY) and peptide YY (PYY) inhibit the contraction of the electrically stimulated mouse vas deferens. Neuropeptides3 (1982) 71–77.
Altschuler, R. A., Parakkal, M.H., Fex, J., Localization of enkephalin-like immunoreactivity in acetylcholinesterase-positive cells in the guinea-pig lateral superior olivary complex that project to the cochlea. Neuroscience9 (1983) 621–630.
Amara, S.G., Jonas, V., Rosenfeld, M.G., Ong, E.S., and Evans, R.M., Alternative RNA-processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature298 (1982) 240–244.
Armstrong, D.M., Miller, R.J., Beaudet, A., and Pickel, V.M., Enkephalin-like immunoreactivity in rat area postrema: Ultrastructural localization and coexistence with serotonin. Brain Res.310 (1984) 269–278
Bartfai, T., Presynaptic aspects of the coexistence of classical neurotransmitters and peptides. TIPS8 (1985) 331–334.
Baumgarten, H.G., Björklund, A., Lachenmayer, L., Nobin, A., and Stenevi, U., Long-lasting selective depletion of brain serotonin by 5,6-dihydroxytryptamine. Acta physiol. scand., Suppl.373 (1971) 1–16.
Beaujouan, J.C., Torrens, Y., Saffroy, M., and Glowinski, J., Quantitative autoradiographic analysis of the distribution of binding sites for (125I) Bolton Hunter derivatives of eledoisin and substance P in the rat brain. Neuroscience18 (1984) 857–875.
Belin, M.F., Weisman-Nanopoulos, D., Steinbusch, H., Verhofstad, A., Maitre, M., Jouvet, M., and Pujol, J.F., Mise en évidence de glutamate décarboxylase et de sérotonine dans un měme neurone au niveau du noyau raphé dorsalis du rat par des méthodes de double marquage immunocytochinique. C.r. Acad. Sci.293 (1981) 337–341.
Belin, M.F., Nanopoulos, D., Didier, M., Aguera, M., Steinbusch, H., Verhofstad, A., Maitre, M., and Pujol, J.F., Immunohistochemical evidence for the presence of γ-aminobutyric acid and serotonin in one nerve cell. A study on the raphe nuclei of the rat using antibodies to glutamate decarboxylase and serotonin. Brain Res.275 (1983) 329–339.
Berod, A., Chat, M., Paut, L., and Tappaz, M., Catecholaminergic and GABAergic anatomical relationship in the rat substantia nigra, locus coeruleus, and hypothalamic median eminence: Immunocytochemical visualization of biosynthetic enzymes on serial semithin plastic-embedded sections. J. Histochem. Cytochem.32 (1984) 1331–1338.
Berkenboesch, F., Linton, E.A., and Tilders, F.J.H., Colocalization of PHI- and CRF-immunoreactivity in neurons of the rat hypothalamus: a surprising artefact. Neuroendocrinology44 (1986) 338–346.
Björklund, A., and Hökfelt, T., Eds, Handbook of Chemical Neuroanatomy, vol. 4; GABA and Neuropeptides in the CNS, Part I. Elsevier, Amsterdam 1985.
Blessing, W.W., Howe, P.R.C., Joh, T.H., Oliver, J.R., and Willoughby, J.O., Distribution of tyrosine hydroxylase and neuropeptide Y-like immunoreactive neurons in rabbit medulla oblongata, with attention to colocalization studies, presumptive adrenaline-synthesizing perikarya, and vagal preganglionic cells. J. comp. Neurol.248 (1986) 285–300.
Branton, W.D., Phillips, H.S., and Jan, Y.N., The LHRH family of peptide messengers in the frog nervous system. in: Progress in Brain Research, pp. 205–215. Eds T. Höpkfelt, K. Fuxe and B. Pernow, Elsevier, Amsterdam 1986.
Brashear, H.R., Záborszky, L., and Heimer, L., Distribution of GABAergic and cholinergic neurons in the rat diagnonal band. Neuroscience17 (1986) 439–445.
Browstein, M.J., Saavedra, J.M., Axelrod, J., and Carpenter, D.O., Coexistence of several putative neurotransmitters in single identified neurons of aplysia. Proc. natn. Acad. Sci. USA71 (1974) 4662–4665.
Buchanan, J.T., Brodin, L., Hökfelt, T., and Grillner, S., Survey of neuropeptide-like immunoreactivity in the lamprey spinal cord. Brain Res., in press.
Burnstock, G., Do some nerve cells release more than one transmitter? Neuroscience1 (1976) 239–248.
Caffé, A.R., and van Leeuwen, F.W., Vasopressin-immunoreactive cells in the dorsomedial hypothalamic region, medial amygdaloid nucleus and locus coeruleus of the rat. Cell Tissue Res.233 (1983) 23–33.
Chan-Palay, V., Combined immunocytochemistry and autoradiography after in vivo injection of monodonal antibody to substance P and3H-serotonin: Coexistence of two putative transmitters in single raphe cells and fiber plexuses. Anat. Embryol.156 (1979) 241–254.
Chan-Palay, V., and Palay, S.L., Eds, Coexistence of Neuroactive Substances in Neurons. John Wiley & Sons, New York 1984.
Chan-Palay, V., Jonsson, G., and Palay, S.L., Serotonin and substance P coexist in neurons of the rat's central nervous system. Proc. natn. Acad. Sci. USA75 (1978) 1582–1586.
Chan-Palay, V., Nilaver, G., Palay, S.L., Beinfeld, M.C., Zimmerman, E.A., Wu, J.-Y., and O'Donohue, T.L., Chemical heterogeneity in cerebellar Purkinje cells: evidence and coexistence of glutamic acid decarboxylase-like and motilin-like immunoreactivities. Proc. natn. Acad. Sci. USA78 (1981) 7787–7791.
Charmay, Y., Léger, L., Dray, F., Bérod, A., Jouvet, M., Pujol, J.F., and Dubois, P.M., Evidence for the presence of enkephalin in catecholaminergic neurons of cat locus coeruleus. Neurosci. Lett.30 (1982) 147–151.
Chubb, I.W., Goodman, S., and Smith, A.D., Is acetylcholinesterase secreted from central neurons into the cerebrospinal fluids? Neuroscience1 (1976) 57–62.
Chubb, I.E., Hodgson, A.J., and White, G.H., Acetylcholinesterase hydrolyzes substance P. Neuroscience5 (1980) 2065–2072.
Coons, A.H., Fluorescent antibody methods, in: General Cytochemical Methods, pp. 399–422. Ed. J.F. Danielli, Academic Press, New York 1958.
Costa, M., and Furness, J.B., Somatostatin is present in subpopulation of noradrenergic nerve fibres supplying the intestine. Neuroscience13 (1984) 911–919.
Costa, M., Furness, J.B., and Gibbins, I.L., Chemical coding of enteric neurons, in: Progress in Brain Research, vol. 68, pp. 217–239. Eds T. Hökfelt, K. Fuxe and B. Pernow. Elsevier, Amsterdam 1986.
Cuello, A.C., Ed., Co-transmission. MacMillan, London and Basingtoke 1982.
Cuello, A.C., Ed., Immunohistochemistry; IBRO Handbook Series: Methods in the Neurosciences, vol. 3. John Wiley & Sons, Chichester 1983.
Cuello, A.C., and Kanazawa, I., The distribution of substance P immunoreactive fibers in the rat central nervous system. J. comp. Neurol.178 (1978) 129–156.
Dahlström, A., Effects of vinblastine and colchicine on monoamine containing neurons of the rat with special regard to the axoplasmic transport of amine granules. Acta neuropath. Suppl.5 (1971) 226–237.
Dahlström, A., and Fuxe, K., Evidence of the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand.62, Suppl. 232 (1964) 1–55.
Dalsgaard, C.-J., Hökfelt, T., Elfvin, L.-G., Skirboll, L., and Emson, P., Substance P-containing primary sensory neurons projecting to the inferior mesenteric ganglion: Evidence from combined retrograde tracing and immunohistochemistry. Neuroscience7 (1982) 647–654.
Dalsgaard, C.-J., Hökfelt, T., Schultzberg, M., Lundberg, J.M., Terenius, L., Dockray, G.J., and Goldstein, M., Origin of peptide-containing fibers in the inferior mesenteric ganglion of the guinea pig: Immunohistochemical studies with antisera to substance P, enkephalin, vasoactive intestinal polypeptide, cholecystokinin and bombesin. Neuroscience9 (1983) 191–211.
Doerr-Schott, J., Multiple immunocytochemical labelling methods for the simutaneous ultrastructural localization of various hypophysial hormones, in: Pars Distalis of the Pituitary Gland-Structure, Function and Regulation. Excerpta Medica Int. Congr. Ser. 673, pp. 95–106. Eds F. Yoshimura and A. Gorbman Elsevier Science Publ., Amsterdam 1986.
Eckenstein, F., and Baughman, R.W., Two types of cholinergic innervation in cortex, one co-localized with vasoactive intestinal polypeptide. Nature309 (1984) 153–155.
Edwards A.V., Järhult, J., Andersson, P.-O., and Bloom, S.R., The importance of the pattern of stimulation in relation to the response of autonomic effectors, in: Systemic Role of Regulatory Peptides, pp. 145–148. Eds S.R. Bloom, J.M. Polak and E. Lindenlaub. Schattauer, Stuttgart 1982.
Everitt, B.J., Hökfelt, T., Terenius, L., Tatemoto, K., Mutt, V., and Goldstein, M., Differential co-existence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system to the rat. Neuroscience11 (1984) 443–462.
Everitt, J.E., Hökfelt, T., Wu, J.-Y., and Goldstein, M., Coexistence of tyrosine hydroxylase-like and gamma-aminobutyric acid-like immunoreactivities in neurons of the arcuate nucleus. Neuroendocrinology39 (1984) 189–191.
Everitt, B.J., Meister, B., Hökfelt, T., Melander, T., Terenius, L., Rökaeus, Å., Theodorsson-Norheim, E., Dockray, G., Edwardson, J., Cuello, C., Elde, R., Goldstein, M., Hemmings, H., Ouimet, C., Walaas, I., Greengard, P., Vale, W., Weber, E., Wu, J.-Y., and Chang, K.-J., The hypothalamic arcuate nucleus-median eminence DARPP-32 with special reference to coexistence in dopamine neurons. Brain Res. Rev.11 (1986) 97–155.
Fibiger, H.C., The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Res. Rev.4 (1982) 327–388.
Fontaine, B., Klarsfeld, A., Hökfelt, T., and Changeux, J.-P., Calcitonin gene-related peptide, a peptide in spinal cord motoneurons, increases the number of acetylcholine receptors in primary cultures of chick embryo myotubes. Neurosci. Lett.71 (1986) 59–65.
Fried, G., Terenius, L., Hökfelt, T., and Goldstein, M., Evidence for the differential localization of noradrenaline and neuropeptide Y (NPY) in neuronal storage vesicles isolated from rat vas deferens. J. Neurosci.5 (1985) 450–458.
Furness, J.B., Costa, M., Emson, P.C., Håkanson, R., Moghimzadeh, E., Sundler, F., Taylor, J.L., and Chance, R.C., Distribution, pathways and reactions to drug treatment of nerves with neuropeptide Y- and pancreatic polypeptidelike immunoreactivity in the guinea pig digestive tract. Cell Tissue Res.234 (1983) 71–92.
Gall, C., Henry, S.H.C., Seroogy, K.B., and Jones, E.G., Colocalization of GABA- and tyrosine hydroxylase-like immunoreactivities in neurons of the rat main olfactory bulb. Soc. Neurosci. Abstr.15 (1985) 89.
Gibson, S.J., Polak, J.M., Bloom, S.r., Sabate, I.M., Mulderry, P.M., Ghatei, M.A., McGregor, G.P., Morrison, J.F.B., Kelly, J.S., Evans, R.M., and Rosenfeld, M.G., Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species. J. Neurosci.4 (1984) 3101–3111.
Gilbert, R.F.T., Emson, P.C., Hunt, S.P., Bennett, G.W., Marsden, C.A., Sandberg, B.E.B., Steinbusch, H., and Verhofstad, A.A.J., The effects of monoamine neurotoxins on peptides in the rat spinal cord. Neuroscience7 (1982) 69–88.
Glazer, E.J., Steinbusch, H., Verhofstad, A., and Basbaum, A.I., Serotonin neurons in nucleus raphe dorsalis and paragigantocellularis of the cat contain enkaphalin, J. Physiol., Paris77 (1981) 241–245.
Greenfield, S.A., The significance of dendritic release of transmitter and protein in the substantia nigra. Neurochem. int.7 (1985) 887–901.
Greenfield, S.A., Cheramy, A., Leviel, V., and Glowinski, J., In vivo release of acetylcholinesterase in the cat substantiae nigrae and caudate nuclei. Nature284(1980) 355–357.
Hendry, S.H.C., Jones, E.G., DeFelipe, J., Schmechel, D., Brandon, C., and Emson, P.C., Neuropeptide-containing neurons of the cerebral cortex are also GABAergic. Proc. natn. Acad. Sci. USA81 (1984) 6526–6530.
Hökfelt, T., Elfvin, L.-G., Elde, R., Schultzberg, M., Goldstein, M., and Luft, R., Occurrence of somatostatin-like immunoreactivity in some peripheral sympathetic noradrenergic neurons. Proc. natn. Acad. Sci. USA74 (1977) 3587–3591.
Hökfelt, T., Ljungdahl, Å., Steinbusch, H., Verhofstad, A., Nilsson, G., Brodin, E., Pernow, B., and Goldstein, M., Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine-containing neurons in the rat central nervous system. Neuroscience3 (1978) 517–538.
Hökfelt, T., Johansson, O., Ljungdahl, Å., Lundberg, J.M., and Schultzberg, M., Peptidergic neurons. Nature284 (1980) 515–521.
Hökfelt, T., Lundberg, J.M., Schultzberg, M., Johansson, O., Ljungdahl, Å., and Rehfeld, J., Coexistence of peptides and putative transmitters in neurons, in: Neural Peptides and Neuronal Communication, pp. 1–23. Eds E. Costa and M. Trabucchi. Raven Press, New York 1980.
Hökfelt, T., Rehfeld, J.F., Skirboll, L., Ivemark, B., Goldstein, M., and Markey, K., Evidence for coexistence of dopamine and CCK in mesolimbic neurones. Nature285 (1980) 476–478.
Hökfelt, T., Skirboll, L., Rehfeld, J.F., Goldstein, M., Markey, K., and Dann, O., A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contains a cholecystokinin-like peptide: evidence from immunohistochemistry combined with retrograde tracing. Neuroscience5 (1980) 2093–2124.
Hökfelt, T., Everitt, B.J., Theodorsson-Norheim, E., and Goldstein, M., Occurrence of neurotensinlike immunoreactivity in subpopulations of hypothalamic, mesencephalic, and medullary catecholamine neurons. J. comp. Neurol.222 (1984) 543–559.
Hökfelt, T., Lundberg, J.M., Lagercrantz, H., Tatemoto, K., Mutt, V., Lundberg, J.M., Terenius, L., Everitt, B.J., Fuxe, K., Agnati, L.F., and Goldstein, M., Occurrence of neuropeptide Y (NPY)-like immunoreactivity in catecholamine neurons in the human medulla oblongata. Neurosci. Lett.36 (1983) 217–222.
Hökfelt, T., Johansson, O., and Goldstein, M., Central catecholamine neurons as revealed by immunohistochemistry with special reference to adrenaline neurons, in: Handbook of Chemical Neuroanatomy, vol. 2: Classical Transmitters in the CNS, Part I, pp. 157–276. Eds A. Björklund and T. Hökfelt. Elsevier, Amsterdam 1984.
Hökfelt, T., Johansson, O., and Goldstein, M., Chemical anatomy of the brain. Science225 (1984) 1326–1334.
Hökfelt, T., Mårtensson, R., Björklund, A., Kleinau, S., and Goldstein, M., Distributional maps of tyrosine hydroxylase immunoreactive neurons in the rat brain, in: Handbook of Chemical Neuroanatomy, vol. 2: Classical Transmitters in the CNS, Part I, pp. 277–379. Eds A. Björklund and T. Hökfelt. Elsevier, Amsterdam 1984.
Hökfelt, T., Skirboll, L., Everitt, B.J., Meister, B., Brownstein, M., Jacobs, T., Faden, A., Kuga, S., Goldstein, M., Markstein, R., Dockray, G., and Rehfeld, J., Distribution of cholecystokinin-like immunoreactivity in the nervous system with special reference to coexistence with classical neurotransmitters and other neuropeptides, in: Neuronal Cholecystokinin, pp. 255–274. Eds J.J. Vanderhaeghen and J. Crawley. Ann. N.Y. Acad. Sci. New York 1985.
Hökfelt, T., Fuxe, K., and Pernow, B., Eds, Coexistence of neuronal messengers: a new principle in chemical transmission, in: Progress in Brain Research, vol. 68. Elsevier, Amsterdam 1986.
Hökfelt, T., Holets, V.R., Staines, W., Meister, B., Melander, T., Schalling, M., Schutzberg, M., Freedman, J., Björklund, H., Olson, L., Lindh, B., Elfvin, L.-G., Lundberg, J.M., Lindgren, J.Å., Samuelsson, B., Pernow, B., Terenius, L., Post, C., Everitt, B., and Goldstein, M., Coexistence of neuronal messengers — an overview, in: Progress in Brain Research, vol. 68, pp. 33–70. Eds T. Hökfelt, K. Fuxe and B. Pernow, Elsevier, Amsterdam 1986.
Hökfelt, T., and Terenius, L., More on receptor mismatch. TINS10 (1987) 22.
Hunt, S.P., and Lovick, T.A., The distribution of serotonin, metenkephalin and β-lipotropin-like immunoreactivity in neuronal perikarya of the cat brain stem. Neurosci. Lett.30 (1982) 139–145.
Hylden, J.L.K., and Wilcox, G.L., Intrathecal substance P elicits caudally-directed biting and scratching behavior in mice. Brain Res.217 (1981) 212–215.
Ibata, Y., Fukui, K., Okamura, H., Kawakami, T., Tanaka, M., Obata, H.L., Isuto, T., Terubayashi, H., Yanaihara, C., and Yanaihara, N., Coexistence of dopamine and neurotensin in the hypothalamic arcuate and periventricular nucleus. Brain Res.269 (1983) 177–179.
Jacobowitz, D.M., and Palkovits, M., Topographic atlas of catecholamine and acetylcholinesterase-containing neurons in the rat brain. I. Forebrain (Telencephalon, Diencephalon). J. comp. Neurol.157 (1974) 13–28.
Jirikowski, G., Reisert, I., Pilgrim, Ch., and Oertel, W.H., Coexistence of glutamate decarboxylase and somatostatin immunoreactivity in cultured hippocampal neurons of the rat. Neurosci. Lett.46 (1984) 35–39.
Johansson, O., Hökfelt, T., Pernow, B., Jeffcoate, S.L., White, N., Steinbusch, H.W.M., Verhofstad, A.A.J., Emson, P.C., and Spindel, E., Immunohistochemical support for three putative transmitters in one neuron: coexistence of 5-hydroxytryptamine-, substance P-, and thyrotropin releasing hormone-like immunoreactivity in medullary neurons projecting to the spinal cord. Neuroscience6 (1981) 1857–1881.
Ju, G., Hökfelt, T., Fischer, J.A., Frey, P., Rehfeld, J.F., and Dockray, G.J., Does cholecystokinin-like immunoreactivity in rat primary sensory neurons represent calcitonin gene related peptide? Neurosci. Lett.68 (1986) 305–310.
Köhler, C., Swanson, L.W., Haglund, L., and Wu, J.-Y., The cytoarchitecture, histochemistry and projections of the tuberomammillary nucleus in the rat. Neuroscience16 (1985) 85–110.
Kondo, H., Kuramoto, H., Wainer, B.H., and Yanaihara, N., Evidence for the coexistence of acetylcholine and enkephalin in the sympathetic preganglionic neurons of rats. Brain Res.335 (1985) 309–314.
Kosaka, T., Hataguchi, Y., Hama, K., Nagatsu, I., and Wu, J.-Y., Coexistence of immunoreactivities for glutamate decarboxylase and tyrosine hydroxylase in some neurons in the periglomerular region of the rat main olfactory bulb: possible coexistence of gamma-aminobutyric acid (GABA) and dopamine. Brain Res.343 (1985) 166–171.
Kosaka, T., Kosaka, K., Tateishi, K., Hamaoka, Y., Yanaihara, N., Wu, J.-Y., and Hama, K., GABAergic neurons containing CCK-8-like and/or VIP-like immunoreactivities in the rat hippocampus and dentate gyrus. J. comp. Neurol.239 (1985) 420–430.
Krieger, D.T., Brownstein, M.J., and Martin, J.B., Eds, Brain Peptides. John Wiley & Sons, New York 1983.
Léger, L., Charnay, Y., Chayvialle, J.A., Bérod, A., Dray, F., Pujol, J.F., Jouvet, M., and Dubois, P.M., Localization of substance P-and enkephalin-like immunoreactivity in relation to catecholamine-containing cell bodies in the cat dorsolateral pontine tegmentum: an immunofluorescence study. Neuroscience8 (1983) 525–546.
Le Grevés, P., Nyberg, F., Terenius, L., and Hökfelt, T., Calcitonin gene-related peptide is a potent inhibitor of substance P degradation. Eur. J. Pharmac.115 (1986) 309–311.
Lindh, B., Hökfelt, t., Elfvin, G., Terenius, L., Fahrenkrug, J., Elde, R., and Goldstein, M., Topography of NPY-, somatostatin-, and VIP-immunoreactive, neuronal subpopulations in the guinea pig celiac-superior mesenteric ganglion and their projection to the pylorus. J. Neurosci.6 (1986) 2371–2383.
Ljungdahl, Å, Hökfelt, T., and Nilsson, G., Distribution of substance P-like immunoreactivity in the central nervous system of the rat. I. Cell bodies and nerve terminals. Neuroscience3 (1978) 861–943.
Lorenz, R.G., Saper, C.B., Wong, D.L., Ciaranello, R.D., and Loewy, A.D., Co-localization of substance P- and phenylethanolamine-N-methyltransferase-like immunoreactivity in neurons of ventrolateral medulla that project to the spinal cord: Potential role in control of vasomotor tone. Neurosci. Lett.55 (1985) 255–260.
Lovick, T.A., and Hunt, S.P., Substance P-immunoreactive and serotonin-containing neurones in the ventral brainstem of the cat, Neurosci. Lett.36 (1983) 223–228.
Lundberg, J.M., and Hökfelt, T., Coexistence of peptides and classical neurotransmitters. TINS6 (1983) 325–333.
Lundberg, J.M., and Hökfelt, T., Multiple co-existence of peptides and classical transmitters in peripheral autonomic and sensory neurons-functional and pharmacological implications, in: Progress in Brain Research, vol. 68, pp. 241–262. Eds T. Hökfelt, K. Fuxe and B. Pernow. Elsevier, Amsterdam 1986.
Lundberg, J.M., and Tatemoto, K., Pancreactic polypeptide family (APP, BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to α-adrenoceptor blockade. Acta physiol. scand.116 (1982) 393–402.
Lundberg, J.M., Fried, G., Fahrenkrug, J., Holmstedt, B., Hökfelt, T., Lagercrantz, H., Lundgren, G., and Änggård, A., Subcellular fractionation of cat submandibular gland: comparative studies on the distribution of acetylcholine and vasoactive intestinal polypeptide (VIP). Neuroscience6 (1981) 1001–1010.
Lundberg, J.M., Hedlund, B., Änggård, A., Fahrenkrug, J., Hökfelt, T., Tatemoto, K., and Bartfai, T., Co-storage of peptides and classical transmitters in neurons, in: Systemic Role of Regulatory Peptides, pp. 93–119. Eds S.R. Bloom, J.M. Polak and E. Lindenlaub. Schattauer, Stuttgart and New York 1982.
Lundberg, J.M., Hökfelt, T., Änggård, A., Terenius, L., Elde, R., Markey, K., Goldstein, M., and Kimmel, J., Organizational principles in the peripheral sympathetic nervous system: subdivision by coexisting peptides (somatostatin-, avian pancreatic polypeptide-, and vasoactive intestinal polypeptide-like immunoreactive materials). Proc. natn. Acad. Sci. USA79 (1982) 1303–1307.
Lundberg, J.M., Terenius, L., Hökfelt, T., Martling, C.R., Tatemoto, K., Mutt, V., Polak, J., Bloom, S., and Goldstein, M., Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta physiol. scand.116 (1982) 477–480.
Macrae, I.M., Furness, J.B., and Costa, M., Distribution of sub-groups of noradrenaline neurons in the coeliac ganglion of the guinea-pig. Cell Tissue Res.244 (1986) 173–180.
Mantyh, P.W., and Hunt, S.P., Evidence for cholecystokininlike immunoreactive neurons in the rat medulla oblongata which project to the spinal cord. Brain Res.291 (1984) 49–54.
Mason, R.T., Peterfreund, R.A., Sawchenko, P.E., Corrigan, A.Z., Rivier, J.E., and Vale, W.W., Release of the predicted calcitonin gene-related peptide from cultured rat trigeminal ganglion cells. Nature308 (1984) 653–655.
Matthews, M.R., and Cuello, A.C., Substance P-immunoreactive peripheral branches of sensory neurones innervate guinea-pig sympathetic neurons. Proc. natn. Acad. Sci. USA79 (1982) 1668–1672.
Matthysse, S.W., and Kety, S.S., Eds, Catecholamines and Schizophrenia. Pergamon Press, Oxford 1975.
Meister, B., Hökfelt, T., Vale, W.W., and Goldstein, M., Growth hormone releasing factor (GRF) and dopamine coexist in hypothalamic arcuate neurons. Acta physiol. scand.124 (1985) 133–136.
Meister, B., Hökfelt, T., Vale, W.W., Sawchenko, P.E., Swanson, L., and Goldstein, M., Coexistence of dopamine and growth hormone releasing factor (GRF) in a subpopulation of tubero-infundibular neurons of the rat. Neuroendocrinology42 (1986) 237–247.
Meister, B., Hökfelt, T., Brown, J., Joh, T., and Goldstein, M., Dopaminergic cells in the caudal A13 cell group express somatostatin-like immunoreactivity. Exp. Brain Res., 1987, in press.
Melander, T., Staines, W.A., Hökfelt, T., Rökaeus, Å., Eckenstein, F., Salvaterra, P.M., and Wainer, B.H., Galanin-like immuno-reactivity in cholinergic neurons of the septum-basal forebrain complex projecting to the hippocampus of the rat. Brain Res.360 (1985) 130–138.
Melander, T., and Staines, W.A., A galanin-like peptide coexists in putative cholinergic somata of the septum-basal forebrain complex and in acetylcholinesterase-containing fibers and varicosities within the hippocampus in the owl monkey (Aotus trivirgatus). Neurosci. Lett.68 (1986) 17–22.
Melander, T., Hökfelt, T., Rökaeus, Å., Cuello, A.C., Oertel, W.H., Verhofstad, A., and Goldstein, M., Coexistence of galanin-like immunoreactivity with catecholamines, 5-hydroxytryptamine, GABA and neuropeptides in the rat CNS. J. Neurosci.6 (1987) 3640–3654.
Millhorn, D.E., Hökfelt, T., Seroogy, K., Oertel, W., Verhofstad, A., and Wu, J.-Y., Immunohistochemical evidence for colocalization of gamma-aminobutyric acid (GABA) and serotonin in neurons of the ventral medulla oblongata projecting to the spinal cord. Brain Res. (1987) in press.
Millhorn, D., Hökfelt, T., Terenius, L., Buchan, A., and Brown, J.C., Somatostatin- and enkephalin-like immunoreactivities are frequently colocalized in neurons in the caudal brain stem of the rat. Exp. Brain. Res., 1987, in press.
Mishkin, M., A memory system in the monkey. Phil. Trans. R. Soc. Lond. Biol. Ser.B 298 (1982) 85–95.
Nairn, R.C., Ed. Fluorescent Protein Tracing, 3rd edition. E. & S. Livingstone Ltd., Edinburgh and London 1969.
Nakane, P.K., Simultaneous localization of multiple tissue antigens using the peroxidase-labeled antibody method: a study in pituitary glands of the rat. J. Histochem. Cytochem.16 (1968) 557–560.
New H.V., and Mudge, A.W., Calcitonin gene-related peptide regulates muscle acetylcholine receptor synthesis. Nature323 (1986) 809–811.
Nilsson, J., von Euler, A.M., and Dalsgaard, C.-J., Stimulation of connective tissue cell growth by substance P and substance K. Nature315 (1985) 61–63.
Nordström, Ö. Melander, T., Hökfelt, T., Bartfai T., and Goldstein, M., Evidence for an inhibitory effect of the peptide galanin on dopamine release from the rat median eminence. Neurosci. Lett.73 (1987) 21–26.
O'Donohue, T.L., Millington, W.R., Handelmann, G.E., Contreras, P.C., and Chronwall, B.M., On the 50th anniversary of Dale's law: Multiple neurotransmitter neurons. TIPS6 (1985) 305–308.
Oertel, W.H., and Mugnaini, E., Immunocytochemical studies of GABAergic neurons in rat basal ganglia and their relations to other neuronal systems. Neurosci. Lett.47 (1984) 233–238.
Oertel, W.H., Graybiel, A.M., Mugnaini, E., Elde, R.P., Schmechel, D.E., and Kopin, E.J., Coexistence of glutamic acid decarboxylase-and somatostatin-like immunoreactivity in neurons of the feline nucleus reticularis thalami. J. Neurosci.3 (1983) 1322–1332.
Okamura, H., Murakami, S., Chihara, K., Nagatsu, I., and Ibata, Y., Coexistence of growth hormone releasing factor-like and tyrosine hydroxylase-like immunoreactivities in neurons of the rat arcuate nucleus. Neuroendocrinology41 (1985) 177–179.
Osborne, N.N., Is Dale's principle valid? TINS2 (1979) 73–75.
Osborne, N.N., Ed., Dale's Principle, and Communication between Neurones. Pergamon Press, Oxford and New York 1983.
Osborne, N.N., and Beaton, D.W., Direct histochemical localisation of 5,7-dihydroxytryptamine and the uptake of serotonin by a subpopulation of GABA neurones in the rabbit retina. Brain Res.382 (1986) 158–162.
Otsuka, M., and Takahashi, T., Putative peptide neurotransmitters. A. Rev. Pharmac. Toxic.17 (1977) 425–439.
Otsuka, M., Konishi, S., Yanagisawa, M., Tsunoo, A., and Akagi, H., Role of substance P as a sensory transmitter in spinal cord and sympathetic ganglia, in: Substance P in the Nervous System, pp. 13–34. Ciba Foundation Symposium 91. Pitman, London 1982.
Ottersen, O.P., Storm-Mathisen, J., Laake, J.H., and Madsen, S., Distribution of possible amino acid transmitters and some cellular markers in the cerebellum. Neurosci. Lett. Suppl.26, (1986) 399.
Owman, Ch., Håkanson, R., and Sundler, F., Occurrence and function of amines in polypeptides hormones producing cells. Fedn Proc. Fedn. Am. Soc. exp. Biol.32 (1973) 1785–1791.
Palkovits, M., and Jacobowitz, D.M., Topographic atlas of catecholamine and acetylcholinesterase-containing neurons in the rat brain. II. Hindbrain (Mesencephalon, Rhombencephalon). J. comp. Neurol.157 (1974) 29–41.
Palkovits, M., and Brownstein, M.J., Distribution of neuropeptides in the central nervous system using biochemical micromethods, in: Handbook of Chemical Neuroanatomy, vol. 4: GABA and Neuropeptides in the CNS, Part 1, pp 1–71. Eds A. Björklund and T. Hökfelt. Elsevier, Amsterdam 1985.
Pelletier, G., Steinbusch, H.W., and Verhofstad, A., Immunoreactive substance P and serotonin present in the same dense core vesicles. Nature293 (1981) 71–72.
Pearse, A.G.E., The cytochemistry and ultrastructure of polypeptide hormone producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J. Histochem. Cytochem.17 (1969), 303–313.
Pernow, B., Substance P., Pharmac. Rev.35 (1983) 85–141.
Piercey, M.F., Dobry, P.J.K., Schroeder, L.A., and Einspahr, F.J., Behavioral evidence that substance P may be a spinal cord sensory neurotransmitter Brain Res.210 (1981) 407–412.
Polak, J.M., and Van Noorden, S., Ed., Immunocytochemistry. Practical Applications in Pathology and Biology. Wright — PSG, Bristol 1983.
Rosenfeld, M.G., Mermod, J.-J., Amara, S.G., Swanson, L.W., Sawchenko, P.E., Rivier, J., Vale, W.W., and Evans, R.M., Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature304 (1983) 129–135.
Rothman, R.B., Herkenham, M., Pert, C.B., Liang, T., and Cascieri, M.A., Visualization of rat brain receptors for the neuropeptide, substance P. Brain Res.309 (1984) 47–54.
Saria, A., Gamse, R., Petermann, J., Fischer, J.A., Theodorsson-Norheim, E., and Lundberg, J.M., Simultaneous release of several tachykinins and calcitonin gene-related peptide from rat spinal cord slices. Neurosci. Lett.63 (1986) 310–314.
Sawchenko, P.E., Swanson, L.W., Grzanna, R., Howe, P.R.C., Polak, J.M., and Bloom, S.R., Co-localization of neuropeptide-Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J. comp. Neurol.241 (1985) 138–153.
Schmechel, D.E., Vickrey, B.G., Fitzpatrick, D., Elde, R.P., GABAergic neurons of mammalian cerebral cortex: widespread subclass defined by somatostatin content. Neurosci. Lett.47 (1984) 227–232.
Shults, C.W., Quirion, R., Chronwall, B., Chase, T.N., and O'Donohue, T., A comparison of the anatomical distribution of substance P and substance P receptors in the rat central nervous system. Peptides5 (1984) 1097–1128.
Senba, E., Daddona, P.E., Watanabe, T., Wu, J.-Y., and Nagy, J.I., Coexistence of adenosine deaminase, histidine decarboxylase, and glutamate decarboxylase in hypothalamic neurons of the rat. J. Neurosci.5 (1985) 3393–3402.
Smith, A.D., Dale's principle today: Adrenergic tissues, in: Neuron Concept Today. Eds, J. Szentágothai, J. Hámori and E.S. Vizi. Symposium, Tihany, Akadémiai Kiado, Budapest 1976.
Snyder, S., Brain peptides as neurotransmitters. Science209 (1980) 976–983.
Sofroniew, M.V., Pearson, R.C.A., Eckenstein, F., Cuello, A.C., and Powell, T.P.S., Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage. Brain Res.289 (1983) 370–374.
Somogyi, P., Hodgson, A.J., Smith, A.D., Nunzi, M.G., Gorio, A., and Wu, J.-Y., Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin-or cholecystokinin-immunoreactive material. J. Neurosci.4 (1984) 2590–2603.
Staines, W.A., Meister, B., Melander, T., Nagy, J.I., and Hökfelt, T., Three-colour immunohistofluorescence allowing triple labelling within a single section. J. Histochem. Cytochem., 1987, in press.
Sternberger, L.A., Ed., Immunocytochemistry, 2nd edition John Wiley & Sons, New York 1979.
Stjärne, L., and Lundberg, J.M., Neuropeptide Y (NPY) depresses the secretion of3H-noradrenaline and the contractile response evoked by field stimulation in rat vas deferens. Acta physiol. scand.120 (1984) 477–479.
Takami, K., Kawai, Y., Shiosaka, S., Lee, Y., Girgis, S., Hillyard, C.J., MacIntyre, I., Emson, P.C., and Tohyama, M., Immunohistochemical evidence for the coexistence of calcitonin gene-related peptide-and choline acetyltransferase-like immunoreactivity in neurons of the rat hypoglossal, facial and ambiguous nuclei. Brain Res.328 (1985) 386–389.
Takami, K., Kawai, Y., Uchida, S., Tohyama, M., Shiotani, Y., Yoshida, H., Emson, P.C., Girgis, S., Hillyard, C.J., and MacIntyre, J., Effect of calcitonin gene-related peptide on contraction of striated muscle in the mouse. Neurosci. Lett.60 (1985) 227–230.
Tatemoto, K., Röckaeus, Å., Jörnvall, H., McDonald, T.J., and Mutt, V., Galanin—A novel biologically active peptide from porcine intestine. FEBS Lett164 (1983) 124–128.
Thoenen, H., and Tranzer, J.P., Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Arch. Pharmak. exp. Path.261 (1968) 271–288.
Tramu, G., Pillez, A., and Leonardelli, J., An efficient method of antibody elution for the successive or simultaneous location of two antigens by immunocytochemistry. J. Histochem. Cytochem.26 (1978) 322–324.
Triller, A., Cluzeaud, F., and Korn, H. GABA-containing terminals can be opposed to glycine receptors at central synapses. Brain Res. (1987) in press.
Vincent, S.R., Satoh, K., Armstrong, D.M., and Fibiger, H.C., Substance P in the ascending cholinergic reticular system. Nature306 (1983) 688–691.
Wainer, B.H., Levey, A.I., Mufson, E.J., and Mesulam, M.M., Cholinergic systems in mammalian brain identified with antibodies against choline acetyltransferase. Neurochem. Int.6 (1984) 163–182.
Wall, P.D., and Fitzgerald, M., It substance P fails to fulfil the criteria as a neurotransmitter in somatosensory afferents, what might be its function?, in: Substance P in the Nervous System, pp. 249–266. Ciba Foundation Symposium 91, Pitman, London 1982.
Watt, C.B., Su, Y.T., and Lam, D.M.-K., Interactions between enkephalin and GABA in avian retina. Nature311 (1984) 761–763.
Weiler, R., and Ball, A.K., Co-localization of neurotensin-like immunoreactivity and3H-glycine uptake system in sustained amacrine cells of turtle retina. Nature311 (1984) 759–761.
Whitehouse, P.J., Price, D.L., Strable, R.G., Clark, A.W., Coyle, J.T., and DeLong, M.R., Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science215 (1982) 1237–1239.
Wiesenfeld-Hallin, Z., Hökfelt, T., Lundberg J.M., Forssmann, W.G., Reinecke, M., Tschopp, F.A., and Fischer, J.A., Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioural responses of the rat. Neurosci. Lett.52 (1984) 199–204.
Zahm, D.S., Zaborszky, L., Alones, V.E., and Heimer, L., Evidence for the coexistence of glutamate decarboxylase and met-enkephalin immunoreactivities in axon terminals of rat ventral pallidum. Brain Res.325 (1985) 317–321.
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Hökfelt, T., Millhorn, D., Seroogy, K. et al. Coexistence of peptides with classical neurotransmitters. Experientia 43, 768–780 (1987). https://doi.org/10.1007/BF01945354
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DOI: https://doi.org/10.1007/BF01945354