Abstract
Secretoneurin is a newly discovered peptide found in high concentrations in brain. We have studied the release of secretoneurin and noradrenaline from superfused hypothalamic slices from rat brain. Both electrical stimulation and potassium induced depolarisation released secretoneurin and noradrenaline from these slices in a calcium-dependent manner. Electrical stimulation caused a preferential release of noradrenaline when compared to the secretion elicited by high potassium. The time course of secretoneurin release was more protracted than that of noradrenaline. The calcium channel blocker ω-conotoxin inhibited only the electrically induced release of noradrenaline, whereas nifedipine inhibited only that of secretoneurin. These results establish that secretoneurin is secreted from neurons. Inhibition of this release by nifedipine is consistent with the concept that secretion from large dense core vesicles occurs at sites different from that of small vesicles and depends on calcium influx via L-type calcium channels.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bartfai T, Iverfeldt K, Fisone G (1988) Regulation of the release of coexisting neurotransmitters. Ann Rev Pharmacol Toxicol 28:285–310
Bean AJ, Roth RH (1991) Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors. J Neuroscience 11:2694–2702
Blaschko H, Comline RS, Schneider FH, Silver M, Smith AD (1967) Secretion of a chromaffin granule protein; chromogranin, from the adrenal gland by splanchnik nerve stimulation. Nature 215:58–59
Cazalis M, Dayanithi G, Nordmann JJ (1987) Hormone release from isolated nerve endings of the rat neurohypophysis. J Physiol 390:55–70
Clasbrummel B, Osswald H, Illes P (1989) Inhibition of noradrenaline release by ω-conotoxin GVIA in the rat tail artery. Br J Pharmacol 96:101–110
Dooley DJ, Lupp A, Hertting G, Osswald H (1988) ω-conotoxin GVIA and pharmacological modulation of hippocampal noradrenaline release. Eur J Pharmacol 148:61–267
Edmonds B, Klein M, Dale N, Kandel ER (1990) Contributions of two types of calcium channels to synaptic transmission and plasticity. Science 250:1142–1147
Fischer-Colbrie R, Hagn C, Kilpatrick L, Winkler H (1986) Chromogranin C: a third component of the acidic proteins in chromaffin granules. J Neurochem 47:318–321
Gerdes HH, Phillips E, Huttner WB (1988) The primary structure of rat secretogranin II deduced from a cDNA sequence. Nucleic Acids Res 16:11811
Herdon H, Nahorski SR (1989) Investigations of the roles of dihydropyridine and ω-conotoxin-sensitive calcium channel in mediating depolarisation-evoked endogenous dopamine release from striatal slices. Naunyn Schmiedebergs Arch Pharmacol 340:36–40
Hirning LD, Fox AP, Mccleskey EM, Olivera BM, Thayer SA, Miller RJ, Tsien RW (1988) Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science 239:57–61
Hökfelt T (1991) Neuropeptides in perspective: The last ten years. Neuron 7:867–879
Kagotany Y, Picart R, Barret A, Wiedermann B, Huttner WB, Tixier-Vidal A (1991) Subeellular localization of secretogranin II and synaptophysin by immunoelectron microscopy in differentiated hypothalamic neurons in culture. J Histochem Cytochem 39: 1507–1518
Kirchmair R, Hogue-Angeletti R, Gutierrez J, Fischer-Colbrie R, Winkler H (1993) Secretoneurin — a neuropeptide generated in brain, adrenal medulla and other endocrine tissues by proteolytic processing of secretogranin II (chromagranin (c)) Neuroscience 53:359–365
Klein RL, Thureson-Klein ÅK (1990) Neuropeptide co-storage and exocytosis by neuronal large dense-cored vesicles: How good is the evidence? In: Osborne NN (ed) Current aspects of the neurosciences. McMillan Press, pp 219–258
Llinas R, Sugimori M, Lin JW, Cherksey B (1989) Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison. Proc Natl Acad Sci USA 86:1689–1693
Llinas R, Sugimori M, Silver RB (1992) Presynaptic calcium concentration microdomains and transmitter release. J Physiol Paris 86:135–138
Lundy PM, Frew R, Fuller TW, Hamilton MG (1991) Pharmacological evidence for an ω-conotoxin, dihydropyridine-insensitive neuronal Ca2+ channel. Eur J Pharmacol 206:61–68
Maggi CA, Patacchini R, Santicioli P, Lippe IT, Giuliani S, Geppetti P, Del Bianco E, Selleri S, Meli A (1988) The effect of ω-conotoxin GVIA, a peptide modulator of the N-type voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves. Naunyn Schmiedebergs Arch Pharmacol 338:107–113
Mahata SK, Mahata M, Steiner HJ, Fischer-Colbrie R, Winkler H (1992) In situ hybridization: mRNA levels of secretogranin II, neuropeptides and carboxypeptidase H in brains of salt-loaded and brattleboro rats. Neuroscience 48:669–680
Mahata SK, Mahata M, Hortnagl H, Fischer-Colbrie R, Steiner HJ, Dietze O, Winkler H (1993) Concomitant changes of messenger ribonucleic acid levels of secretogranin II, VGF, vasopressin and oxytocin in the paraventricular nucleus of rats after adrenalectomy and during lactation. J Neuroendocrinol 5:323–330
Marksteiner J, Kirchmair R, Mahata SK, Mahata M, Fischer-Colbrie R, Hogue-Angeletti R, Saria A, Winkler H (1993) Distribution of secretoneurin, a peptide derived from secretogranin II, in rat brain: an immunocytochemical and radioimmunological study. Neuroscience 54:923–944
Martin JL, Magistretti PJ (1989) Pharmacological studies of voltage-sensitive Ca2+ channels involved in the release of vasoactive intestinal peptide evoked by K+ in mouse cerebral cortical slices. Neuroscience 30:423–431
Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235:46–52
Neuman B, Wiedermann C, Fischer-Colbrie R, Schober M, Sperk G, Winkler H (1984) Biochemical and functional properties of large and small dense-cored vesicles ins sympathetic nerves of rat and ox vas deferens. Neuroscience 13:921–931
Peng Y, Horn JP (1991) Continuous repetitive stimuli are more effective than bursts for evoking LHRH release in bullfrog sympathetic ganglia. J Neurosci 11:85–95
Peng Y, Zucker RS (1993) Release of LHRH is linearly related to the time integral of presynaptic Ca2+ elevation above a threshold level in bullfrog sympathetic ganglia. Neuron 10:465–473
Perney TM, Hirning LD, Leeman SE, Miller RJ (1986) Multiple calcium channels mediate neurotransmitter release from peripheral neurons. Proc Natl Acad Sci USA 83:6656–6659
Reynolds IJ, Wagner JA, Snyder SH, Thayer SA, Olivera BM, Miller RJ (1986) Brain voltage-sensitive calcium channel subtypes differentiated by ω-conotoxin fraction GVIA. Proc Natl Acad Sci USA 83:8804–8807
Rosa P, Zanini A (1981) Characterization of adenohypophysial polypeptides by twodimensional gel electrophoresis: II. Sulfated and glycosylated polypeptides. Molec Cell Endocrinol 24:181–193
Rosa P, Hille A, Lee RWH, Zanini A, De Camilli P, Huttner WB (1985) Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway. J Cell Biol 101:1999–2011
Saria A, Troger J, Kirchmair R, Fischer-Colbrie R, Hogue-Angeletti R, Winkler H (1993) Secretoneurin releases dopamine from rat striatal slices: a biological effect of a peptide derived from secretogranin II (chromogranin C). Neuroscience 54:1–4
Somogyi P, Hodgson A, De Potter RW, Fischer-Colbrie R, Schober M, Winkler H, Chubb IW (1984) Chromogranin immunoreactivity in the central nervous system. Immunochemical characterization, distribution and relationship to catecholamine and enkephalin pathways. Brain Res Rev 8:193–230
Uchitel OD, Protti DA, Sanchez V, Cherksey BD, Sugimori M, Llinas R (1992) P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses. Proc Natl Acad Sci USA 89:3330–3333
Verhage M, Ghijsen WEJM, Nicholls DG, Wiegant VM (1991a) Characterization of the release of cholecystokinin-8 from isolated nerve terminals and comparison with exocytosis of classical transmitters. J Neurochem 56:1394–1400
Verhage M, McMahon HT, Ghijsen WEJM, Boomsma F, Nicholls DG (1991b) Differential release of amino acids, neuropeptides, and catecholamines from isolated nerve terminals. Neuron 6:517–524
Winkler H, Fischer-Colbrie R (1992) The chromogranins A and B: the first 25 years and future perspectives. Neuroscience 49:497–528
Zhu PC, Thureson-Klein A, Klein RL (1986) Exocytosis from large dense cored vesicles outside the active synaptic zones of terminals within the trigeminal subnucleus caudalis: a possible mechanism for neuropeptide release. Neuroscience 19:43–54
Author information
Authors and Affiliations
Additional information
Correspondence to: H. Winkler at the above address
Rights and permissions
About this article
Cite this article
Troger, J., Kirchmair, R., Marksteiner, J. et al. Release of secretoneurin and noradrenaline from hypothalamic slices and its differential inhibition by calcium channel blockers. Naunyn-Schmiedeberg's Arch. Pharmacol. 349, 565–569 (1994). https://doi.org/10.1007/BF01258460
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01258460