Summary
The regional distribution and the pharmacology of the binding sites labelled with the novel 5-hydroxytryptamine (serotonin) 5-HT1B/1D selective radioligand serotonin-O-carboxy-methyl-glycyl-[125I]tyrosinamide (abbreviated [125I]GTI for the sake of simplicity) was determined using quantitative autoradiography in rat brain. The distribution of [125I]GTI binding sites was largely comparable to that of [125I] iodocyanopindolol ([125I] ICYP) which labels 5-HT1B binding sites (in the presence of 8-OH-DPAT (8-hydroxy-[2N-dipropylamino]tetralin) and isoprenaline, to prevent binding to 5-HT1A and β-adrenoceptor binding sites), although a detailed analysis revealed differences.
The pharmacology of the [125I]GTI binding sites was analysed using compounds known to display high affinity for and/or distinguish between 5-HT1B and 5-HT1D sites: 5-carboxamidotryptamine (5-CT), sumatriptan, CP 93129 (5-hydroxy-3(4-1,2,5,6-tetrahydropyridyl)-4-azaindole), (−)pindolol, PAPP (4[2-[4-[3-(trifluoromethyl)phenyl]-1-piperazinyl]ethyl] benzeneamine), rauwolscine, and 8-OH-DPAT. The displacement of [125I]GTI by 5-CT was monophasic. By contrast, the selective 5-HT1B compound CP 93129 and (−)pindolol produced biphasic curves showing a majority of high affinity sites in the globus pallidus and the substantia nigra, whereas PAPP and sumatriptan (which are somewhat 5-HT1D selective) produced biphasic curves indicating a minority of high affinity sites in these areas. In addition, by blocking the 5-HT1B sites with 100 nM CP 93129, the remaining population of [125I]GTI binding sites could be studied and was found to have high affinity for PAPP, rauwolscine and 8-OH-DPAT. The pharmacological profile of the major binding component was typical of the 5-HT1B type: 5-CT > CP 93129 ⩾ (−)pindolol > sumatriptan >/ PAPP > rauwolscine. The profile of the minor component of [125I] GTI binding is best characterised as that of a 5-HTID site: 5-CT > PAPP ⩾ sumatriptan > rauwolscine > (−)pindolol ⩾ CP 93129.
The localisation of the non 5-HT1B [125I]GTI binding sites was characterised by blocking the 5-HT1B receptors with 100 nM CP 93129. Low densities of the 5-HT1D recognition sites were found to be present in globus pallidus, ventral pallidum, caudate-putamen, subthalamic nucleus, entopeduncular nucleus, substantia nigra (reticular part), nuclei of the (normal and accessory) optic tract, different nuclei of the geniculate body and frontoparietal cortex, although higher densities of 5-HT1B sites were always observed in the same structures. Thus, in agreement with the recent cloning of a rat 5-HT1Dα receptor cDNA, the presence and the distribution of 5-HT1D sites could be documented in rat brain. However, when compared to 5-HT1B sites, 5-HT1D sites represent only a minor component of the [125I]GTI binding in the rat brain structures studied.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Adham N, Romanienko P, Hartig P, Weinshank RL, Branchek T (1992) The rat 5-hydroxytryptamine1B receptor is the species homologue of the human 5-hydroxytryptamine1Dβ receptor. Mol Pharmacol 41:1–7
Amlaiky N, Ramboz S, Boschert U, Plassat J-L, Hen R (1992) Isolation of a mouse “5-HT1E-like” serotonin receptor expressed predominantly in the hippocampus. J Biol Chem 267:19761–19764
Berendsen HHG, Broekkamp CLE (1991) A peripheral 5-HT1D-like receptor involved in serotonergic induced hindlimb scratching in rats. Eur J Pharmacol 194:201–208
Bouhelal R, Smounya L, Bockaert J (1988) 5-HT1B receptors are negatively coupled with adenylate cyclase in rat substantia nigra. Eur J Pharmacol 151:189–196
Boulenguez P, Chauveau J, Segu L, Morel A, Delaage M, Lanoir J (1991) Pharmacological characterization of serotonin-O-carboxymethyl-glycyl-tyrosinamide, a new selective indolic ligand for 5-hydroxytryptamine (5-HT)1B and 5-HT1D binding sites. J Pharmacol Exp Ther 259:1360–1365
Boulenguez P, Segu L, Chauveau J, Morel A, Lanoir J, Delaage M (1992) Biochemical and pharmacological characterization of serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites. J Neurochem 58:951–959
Bruinvels AT, Landwehrmeyer B, Waeber C, Palacios JM, Hoyer D (1991) Homogeneous 5-HT1D recognition sites in the human substantia nigra identified with a new iodinated radioligand. Eur J Pharmacol 202:89–91
Bruinvels AT, Lery H, Nozulak J, Palacios JM, Hoyer D (1992) 5-HT1D binding sites in various species: similar pharmacological profile in calf, guinea-pig, dog, monkey and human brain membranes. Naunyn-Schmiedeberg's Arch Pharmacol 346:243–249
Bruinvels AT, Palacios JM, Hoyer D (1993) 5-Hydroxytryptamine1 recognition sites in rat brain: Heterogeneity of non-5-hydroxytryptamine1A/1C binding sites revealed by quantitative receptor autoradiography. Neuroscience 53:465–473
Dumuis A, Bouhelal R, Sebben M, Cory R, Bockaert J (1988) A non-classical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. Mol Pharmacol 34:880–887
Engel G, Göthert M, Hoyer D, Schlicker E, Hillenbrand K (1986) Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg's Arch Pharmacol 332:1–7
Galzin AM, Poirier MF, Lista A, Chodkiewicz JP, Blier P, Ramdine R, Loo H, Roux FX, Redondo A, Langer SZ (1992) Characterization of the 5-hydroxytryptamine receptor modulating the release of [3H]5-hydroxytryptamine in slices of the human neocortex. J Neurochem 59:1293–1301
Hamblin MW, Metcalf MA (1991) Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol 40:143–148
Hamblin MW, Metcalf MA, McGuffin RW, Karpells S (1992a) Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with a 5-HT1D-like pharmacological specificity. Biochem Biophys Res Commun 184:752–759
Hamblin MW, McGuffin RW, Metcalf MA, Dorsa DM, Merchant KM (1992b) Distinct 5-HT1B and 5-HT1D receptors in rat: structural and pharmacological comparison of the two cloned receptors. Mol Cell Neurosci 3:578–587
Hartig PR (1989) Molecular Biology of 5-HT receptors. Trends Pharmacol Sci 10:64–69
Hartig PR, Branchek TA, Weinshank, RL (1992) A subfamily of 5-HTID receptor genes. Trends Pharmacol Sci 13:152–159
Herrick-Davis K, Titeler M (1988) Detection and characterization of the serotonin 5-HT1D receptor in rat and human brain. J Neurochem 50:1624–1631
Heuring RJ, Peroutka SJ (1987) Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci 7:894–903
Hong JS, Yang HYT, Racagni G, Costa E (1977) Projections of substance P containing neurons from neostriatum to substantia nigra. Brain Res 122:541–544
Hoyer D (1991) The 5-HT receptor family: ligands, distribution and receptor-effector coupling. In: Rodgers RJ, Cooper SJ (eds) 5-HT1A agonists, 5-HT3 antagonists and benzodiazepines: their comparative behavioural pharmacology. Wiley, Chichester, pp 31–57
Hoyer D, Engel G, Kalkman HO (1985) Characterization of the 5-HT1B recognition site in rat brain: binding studies with [125I]iodocyanopindolol. Eur J Pharmacol 118:1–12
Hoyer D, Lery H, Nozulak J, Palacios JM, Bruinvels AT (1992) ‘5-HT1R’ or 5-HT1D binding? Evidence for 5-HT1D binding in rabbit brain. Naunyn-Schmiedeberg's Arch Pharmacol 346:249–255
Hoyer D, Middlemiss DN (1989) The pharmacology of the terminal 5-HT autoreceptors in mammalian brain: evidence for species differences. Trends Pharmacol Sci 10:130–132
Hoyer D, Schoeffter P (1988) 5-HT1D receptors inhibit forskolin-stimulated adenylate cyclase activity in calf substantia nigra. Eur J Pharmacol 147:145–147
Jin H, Oksenberg D, Askenazi A, Peroutka SJ, Duncan AMV, Rozmahel R, Yang Y, Mengod G, Palacios JM, O'Dowd BF (1992) Characterization of the human 5-hydroxytryptamine1B receptor. J Biol Chem 267:5735–5738
Levy FO, Gudermann T, Birnbaumer M, Kaumann AJ, Birnbaumer L (1992) Molecular cloning of a human gene (S31) encoding a novel serotonin receptor mediating inhibition of adenylyl cyclase. FEBS Lett 296:201–206
Limberger N, Deicher R, Starke K (1991) Species differences in presynaptic serotonin autoreceptors: mainly 5-HT1B but possibly in addition 5-HT1D in the rat, 5-HT1D in the rabbit and guinea-pig brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 343: 353–364
Macor JE, Burkhart CA, Heym JH, Ives JL, Lebel LA, Newman ME, Nielsen JA, Ryan K, Schulz DW, Torgersen LK, Koe BK (1990) 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3, 2-b]pyrid-5-one a potent and selective serotonin 5-HT1B agonist and rotationally restricted phenolic analogue of 5 methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole. J Med Chem 33:2087–2093
Maroteaux L, Saudou F, Amlaiky N, Boschert U, Plassat JL, Hen R (1992) The mouse 5HT1B serotonin receptor: cloning, functional expression and localisation in motor control centers. Proc Natl Acad Sci USA 89:3020–3024
Maura G, Raiteri M (1986) Cholinergic terminals in rat hippocampus possess 5-HT1B receptors mediating inhibition of acetycholine release. Eur J Pharmacol 129:333–337
Maura G, Roccatagliata E, Raiteri M (1986) Serotonin autoreceptor in rat hippocampus: Pharmacological characterization as a subtype of the 5-HT1 receptor. Naunyn-Schmiedeberg's Arch Pharmacol 334:323–326
McAllister G, Charlesworth A, Snodin C, Beer MS, Noble AJ, Middlemiss DN, Iversen LL, Whiting P (1992) Molecular cloning of a serotonin receptor from human brain (5-HT1E): a fifth 5-HT1-like subtype. Proc Natl Acad Sci USA 89:5517–5521
Middlemiss DN, Bremer ME, Smith SM (1988) A pharmacological analysis of the 5-HT receptors mediating inhibition of 5-HT release in the guinea-pig frontal cortex. Eur J Pharmacol 157:101–107
Palacios JM, Waeber C, Bruinvels AT, Hoyer D (1992) Direct visualization of serotonin1D receptors in the human brain using a new radioiodinated radioligand. Mol Brain Res 13:175–179
Pazos A, Palacios JM (1985) Quantitative auto- radiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230
Pazos A, Engel G, Palacios JM (1985) Beta-adrenoreceptor blocking agents recognize a subpopulation of serotonin receptors in brain. Brain Res 343:403–408
Pedigo NW, Yamamura HI, Nelson DL (1981) Discrimination of multiple [3H]5-hydroxytryptamine-binding sites by the neuroleptic spiperone in rat brain. J Neurochem 36:220–226
Peroutka SJ (1988) 5-Hydroxytryptamine receptor subtypes: Molecular, biochemical and physiological characterization. Trends Neurosci 11:496–499
Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol 16:687–699
Ribak CE, Vaughn JE, Roberts E (1980) GABAergic nerve terminals decrease in substantia nigra following hemitransections of striatonigral and pallidonigral pathways. Brain Res 192:413–420
Schipper J, Tulp MTM (1988) Serotonin autoreceptors in guinea pig cortex slices resemble the 5-HT1D binding site. Soc Neurosci Abstr 14:552
Schlicker E, Fink K, Göthert M, Hoyer D, Molderings G, Roschke I, Schoeffter P (1989) The pharmacological properties of the presynaptic serotonin autoreceptor in the pig brain cortex conform to the 5-HT1D receptor subtype. Naunyn-Schmiedeberg's Arch Pharmacol 340:45–51
Schoeffter P, Hoyer D (1989) 5-Hydroxytryptamine 5-HT1B and 5-HT1D receptors mediating inhibition of adenylate cyclase activity pharmacological comparison with special reference to the effects of yohimbine rauwolscine and some beta-adrenoceptor antagonists. Naunyn-Schmiedeberg's Arch Pharmacol 340:285–292
Sijbesma H, Schipper J, Cornelissen JCHM, De Kloet ER (1991) Species differences in the distribution of central 5-HT1 binding sites a comparative autoradiographic study between rat and guinea-pig. Brain Res 555:295–304
Vergé D, Daval G, Marcinkiewicz M, Patey A, El Mestikawy S, Gozlan H, Hamon M (1986) Quantitative autoradiography of multiple 5-HT1 receptor subtypes in the brain of control or 5,7-dihydroxytryptamine-treated rats. J Neurosci 6:3474–3482
Voigt MM, Laurie DJ, Seeburg PH, Bach A (1991) Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine 1B receptor. EMBO J 10:4017–4023
Waeber C, Palacios JM (1992) Autoradiographic evidence that non 5-HT1A/5-HT1C [3H]5-HT binding sites are of the 5-HT1B subtype in the hamster and opossum brain, of the 5-HT1D subtype in the rabbit brain. Synapse 12:261–270
Waeber C, Schoeffter P, Palacios JM, Hoyer D (1988) Molecular pharmacology of 5-HT1D recognition sites: radioligand binding studies in human, pig and calf brain membranes. Naunyn Schmiedeberg's Arch Pharmacol 337:595–601
Waeber C, Dietl MM, Hoyer D, Palacios JM (1989a) 5-HT1 receptors in the vertebrate brain. Regional distribution examined by autoradiography. Naunyn-Schmiedeberg's Arch Pharmacol 340:486–494
Waeber C, Schoeffter P, Palacios JM, Hoyer D (1989b) 5- HT(1D) receptors in guinea-pig and pigeon brain. Radioligand binding and biochemical studies. Naunyn-Schmiedeberg's Arch Pharmacol 340:479–485
Weinshank RL, Zgombick JM, Macchi M, Branchek TA, Hartig PR (1992) Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1Dα and 5-HTID1Dβ. Proc Natl Acad Sci USA 89:3630–3634
Zarbin MA, Palacios JM, Wamsley JK, Kuhar MJ (1983) Axonal transport of beta-adrenergic receptors: antero- and retrogradely transported receptors differ in agonist affinity and nucleotide sensitivity. Mol Pharmacol 24:341–348
Author information
Authors and Affiliations
Additional information
Correspondence to: D. Hoyer at the above address
Rights and permissions
About this article
Cite this article
Bruinvels, A.T., Palacios, J.M. & Hoyer, D. Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 347, 569–582 (1993). https://doi.org/10.1007/BF00166939
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00166939