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[3H]sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic study

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Abstract

We have used in vitro autoradiography to visualize [3H]sumatriptan binding sites in sections of guinea-pig and rat brain. In saturation studies, this ligand recognized a single saturable population of high affinity binding sites in all regions examined (pKD = 8.3–9.3). While 5-HT and the sumatriptan derivative CP-122,288 (5-methyl-aminosulfonylmethyl-3-(N-methylpyrrolidin-2R-yl-methyl)-1H-indole) competed for [3H]sumatriptan binding sites with a high affinity and monophasic profile, displacement experiments with 5-carboxamidotryptamine revealed the existence of 2 classes of binding sites. The high affinity component (pKD = 9.2–9.9) probably corresponded to 5-HT1B (rat) or 5-HT1D (guinea-pig) receptors. The intermediate affinity (pKD = 5.7–7.3) of the other component, taken together with their high affinity for [3H]sumatriptan, was similar to that of the cloned 5-HT1F receptor. The regional distribution of the 5-HT1B/1D [3H]sumatriptan binding sites was in agreement with previously published studies (striatonigral system, hypothalamus, central gray, superficial layer of the superior colliculus) and corresponded to the pattern of serotonin-5-O-carboxymethyl-glycyl [125I]tyrosinamide labeling in consecutive sections. [3H]sumatriptan binding sites with a low affinity for 5-CT predominated in the intermediate neocortical layers, the claustrum (in the guinea-pig only), the mammillary nuclei, most of the thalamic nuclei and the principal oculomotor nucleus (in the guinea-pig only). This distribution is very similar to that of 5-HT1F mRNA, indicating further the identity of these sites with 5-HT1F receptors. Very high densities of 5-HT1F sites were also found in the rat parafascicular nucleus.

Some regions, such as the caudate/nucleus, the lateral geniculate nuclei and the spinal trigeminal nucleus appeared to contain both 5-HT1B/1D and 5-HT1F binding sites. Ketanserin had a low affinity for [3H]sumatriptan binding sites in all guinea-pig brain regions, compatible with the presence of the 5-HT1D\ subtype. An exception was the substantia nigra, where a significant proportion of sites displayed an intermediate affinity for this compound, suggesting the presence of 5-HT1Dα receptors. [3H]5-HT labeled 5-HT1F sites in the claustrum and intermediate cortical layers in the guinea-pig. However these data show that [3H]sumatriptan, in the presence of 10 nM 5-carboxamidotryptamine, is a more suitable radioligand to study the distribution of 5-HT1F binding sites.

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References

  • Adham N, Borden LA, Schechter LE, Gustafson EL, Cochran TL, Vaysse P J-J, Weinshank RL, Branchek TA (1993a) Cell-specific coupling of the cloned human 5-HT1F receptor to multiple signal transduction pathways. Naunyn-Schmiedeberg's Arch Pharmacol 348:566–575

    Google Scholar 

  • Adham N, Kao H-T, Schechter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA (1993b) Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to inhibition of adenylate eyclase. Proc Natl Acad Sci USA 90:408–412

    Google Scholar 

  • Allen GV, Hopkins DA (1990) Topography and synaptology of mammilary body projections to the mesencephalon and pons in the rat. J Comp Neurol 301:214–231

    Google Scholar 

  • Amlaiky N, Ramboz S, Boschert U, Plassat J-L, Hen R (1992) Isolation of a mouse 5-HT1E-like serotonin receptor expressed predominantly in hippocampus. J Biol Chem 267:19761–19764

    Google Scholar 

  • Bach AW, Unger L, Sprengel R, Mengod G, Palacios JM, Seeburg PH, Voigt MM (1993) Structure functional expression and spacial distribution of a cloned cDNA encoding a rat 5-HT1D-like receptor. J Recept Res 13:479–502

    Google Scholar 

  • Barone P, Jordan D, Atger F, Kopp N, Fillion G (1994) Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [3H]5-HT in frontal cortex and the hippocampal region of the human brain. Brain Res 638:85–94

    Google Scholar 

  • Beer MS, Middlemiss DN (1993) Serotonin-5-O-carboxymethylglycyl[125I]tyrosinamide labels the 5-HT1D\ receptor subtype in human cortex. Eur J Pharmacol 242:195–198

    Google Scholar 

  • Beer MS, Stanton JA, Bevan Y, Chauhan NS, Middlemiss DN (1992) An investigation of the 5-HTID receptor binding affinity of 5-hydroxytryptamine, 5-carboxyamidotryptamine and sumatriptan in the central nervous system of seven species. Eur J Pharmacol 213:193–197

    Google Scholar 

  • Beer MS, Stanton JA, Hawkins LM, Middlemiss DN (1993) 5-carboxamidotryptamine-insensitive 5-HT1-like receptors are concentrated in guinea pig but not rat claustrum. Eur J Pharmacol 236:167–169

    Google Scholar 

  • Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986) Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563–576

    Google Scholar 

  • Branchek TA (1993) More serotonin receptors? Curr Biol 3:315–317

    Google Scholar 

  • Bruinvels AT, Lery H, Nozulak J, Palacios JM, Hoyer D (1992a) 5-HT1D binding sites in various species: similar pharmacological profile in dog, monkey, calf, guinea-pig and human brain membranes. Naunyn-Schmiedeberg's Arch Pharmacol 346: 243–248

    Google Scholar 

  • Bruinvels AT, Landwehrmeyer B, Moskowitz MA, Hoyer D (1992b) Evidence for the presence of 5-HT1B receptor messenger RNA in neurons of the rat trigeminal ganglia. Eur J Pharmacol 227:357–359

    Google Scholar 

  • Bruinvels AT, Palacios JM, Hoyer D (1993) Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 347:569–582

    Google Scholar 

  • Bruinvels AT, Landwehrmeyer B, Probst A, Palacios JM, Hoyer D (1994a) A comparative autoradiographic study of 5-HT1D binding sites in human and guinea-pig brain using different radioligands. Mol Brain Res 21:19–29

    Google Scholar 

  • Bruinvels AT, Landwehrmeyer B, Gustafson EL, Durkin MM, Mengod G, Branchek TA, Hoyer D, Palacios JM (1994b) Localization of 5-HT1B, 5-HT1Dα 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain. Neuropharmacology 33:367–386

    Google Scholar 

  • Cortimiglia R, Crescimanno G, Salerno MT, Amato G (1991) The role of claustrum in the bilateral control of frontal oculomotor neurons in the cat. Exp Brain Res 84:471–477

    Google Scholar 

  • Dafny N, Reyes-Vazquez C, Qiao JY (1990) Modification of nociceptively identified neurons in thalamic parafascicularis by chemical stimulation with glutamate, morphine, serotonin and focal dorsal raphe stimulation. Brain Res Bull 24:717–723

    Google Scholar 

  • Del Arco C, Galende I, Pazos A (1993) Autoradiographic mapping of 5-HT1 receptors in the guinea-pig brain with particular reference to the 5-HT1D receptor sites. Naunyn-Schmiedeberg's Arch Pharmacol 347:248–256

    Google Scholar 

  • Doenicke A, Brand J, Perrin VL (1988) GR43175 a novel 5-HT1-like receptor agonist for the acute treatment of severe migraine. Lancet 1:1309–1311

    Google Scholar 

  • Feniuk W, Humphrey PPA, Peren MJ, Connor HE, Whalley ET (1991) Rationale for the use of 5-HT1-like agonists in the treatment of migraine. J Neurol 238:S57-S61

    Google Scholar 

  • Göthert M, Molderings GJ, Fink K, Schlicker E (1991) Heterogeneity of presynaptic serotonin receptors on sympathetic neurones in blood vessels. Blood Vessels 28:11–18

    Google Scholar 

  • Hamblin MW, McGuffin RW, Metcalf MA, Dorsa DM, Merchant KM (1992) Distinct 5-HT1B and 5-HT1D serotonin receptors in rat: structural and pharmacological comparison of the two cloned receptors. Mol Cell Neurosci 3:578–587

    Google Scholar 

  • Hamel E, Fan E, Linville D, Ting V, Villemure J-G, Chia L-S (1993) Expression of mRNA for the serotonin 5-hydroxytryptamine1D\ receptor subtype in human and bovine cerebral arteries. Mol Pharmacol 44:242–246

    Google Scholar 

  • Hartig PR, Branchek TA, Weinshank RL (1992) A subfamily of 5-HT1D receptor genes. Trends Pharmacol Sci 13:152–159

    Google Scholar 

  • Heuring RE, Peroutka SJ (1987) Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci 7:894–903

    Google Scholar 

  • Hoyer D, Schoeffter P, Waeber C, Palacios JM (1990) Serotonin 5-HT1D receptors. Ann NY Acad Sci 600:168–182

    Google Scholar 

  • Hoyer D, Middlemiss DN (1989) Species differences in the pharmacology of terminal 5-HT autoreceptors in mammalian brain. Trends Pharmacol Sci 10:131–132

    Google Scholar 

  • Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PPA (1994) VII. International Union of Pharmacology Classification of Receptors for 5-Hydroxytryptamine (Serotonin). Pharm Rev 46:157–203

    Google Scholar 

  • Kaumann AJ, Frenken M, Posival H, Brown AM (1994) Variable participation of 5-HT1-like receptors and 5-HT2 receptors in serotonin-induced contraction of human isolated coronary arteries: 5-HT1-like receptors resemble cloned 5-HT1D\ receptors. Circulation 90:1141–1153

    Google Scholar 

  • Lee WS, Moskowitz MA (1993) Conformationally restricted sumatriptan analogues CP-122, 288 and CP-122, 638 exhibit enhanced potency against neurogenic inflammation in dura mater. Brain Res 626:303–305

    Google Scholar 

  • Leonhardt S, Herrick-Davis K, Teitler M (1989) Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. J Neurochem 53:465–471

    Google Scholar 

  • Levy FO, Gudermann T, Birnbaumer M, Kauman 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

    Google Scholar 

  • Lovenberg TW, Erlander MG, Baron MG, Racke M, Slone AL, Siegel BW, Craft CM, Burns JE, Danielson PE, Sutcliffe JG (1993) Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Proc Natl Acad Sci USA 90:2184–2188

    Google Scholar 

  • Lowther S, De Paermentier F, Rufus Crompton M, Horton RW (1992) The distribution of 5-HT1D and 5-HT1E binding sites in human brain. Eur J Pharmacol 222:137–142

    Google Scholar 

  • Macor JE, Blank DH, Post RJ, Ryan K (1992) The synthesis of a conformationally restricted analog of the antimigraine drug sumatriptan. Tetrahedron Lett 33:8011–8014

    Google Scholar 

  • 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

    Google Scholar 

  • Miller KJ, Teitler M (1992) Quantitative autoradiography of 5-CT-sensitive (5-HT1D) and 5-CT-insensitive (5-HT1E) serotonin receptors in human brain. Neurosci Lett 136:223–226

    Google Scholar 

  • Moskowitz MA (1992) Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci l3:307–311

    Google Scholar 

  • Neve KA, McGonigle P, Molinoff PB (1986) Quantitative analysis of the selectivity of radioligands for subtypes of beta-adrenergic receptors. J Pharmacol Exp Ther 238:46–53

    Google Scholar 

  • Palacios JM, Waeber C, Bruinvels AT, Hoyer D (1992) Direct vizualization of serotonin1D receptors in the human brain using a new iodinated ligand. Mol Brain Res 13:175–179

    Google Scholar 

  • Parker EM, Grisel DA, Iben LG, Shapiro RA (1993) A single amino acid difference accounts for the pharmacological distinctions between the rat and human 5-hyrdoxytryptamine1B receptors. J Neurochem 60:380–383

    Google Scholar 

  • Peroutka SJ (1991) Cortical and striatal variations in drug competition studies with putative 5-hyrdoxytryptamine1D binding sites. Brain Res 553:206–210

    Google Scholar 

  • Rebeck GW, Maynard KI, Hyman BT, Moskowitz MA (1994) Selective 5-HT1Dα serotonin receptor gene expression in trigeminal ganglia: implications for antimigraine drug development. Proc Natl Acad Sci USA 91:3666–3669

    Google Scholar 

  • Rhodes VLH, Reilly YC, Bruinvels AT (1994) [3H]sumatriptan labels putative 5-HT1F receptor binding sites in the guinea-pig brain. Abstracts of the British Pharmacological Society Meeting, December 1994, P201

  • Schoeffter P, Hoyer D (1989) How selective is GR43175? Interaction with functional 5-HT1A 5-HT1B, 5-HT1C and 5-HT1D receptors. Nauyn-Schmiedeberg's Arch Pharmacol 340:135–138

    Google Scholar 

  • Simpson CW, Ruwe WD, Myers RD (1993) Anatomical distribution of brainstem sites where PGE1 induces hyperthermia in macaque species. Can J Physiol Pharmacol 71:414–424

    Google Scholar 

  • Skingle M, Higgins GA, Feniuk W (1994) Stimulation of central 5-HT1D receptors causes hypothermia in the guinea-pig. J Psychopharmacol 8:14–21

    Google Scholar 

  • Sumner MJ, Humphrey PPA (1989) Heterogeneous 5-HT1D binding sites in porcine brain can be differentiated by GR43175. Br J Pharmacol 98:29–31

    Google Scholar 

  • Waeber C, Schoeffter P, Palacios JM, Hoyer D (1988a) 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

    Google Scholar 

  • Waeber C, Dietl MM, Hoyer D, Probst A, Palacios JM (1988b) Visualization of a novel serotonin recognition site (5-HT1D) in the human brain by autoradiography. Neurosci Lett 88: 11–16

    Google Scholar 

  • 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 340:479–485

    Google Scholar 

  • Waeber C, Schoeffter P, Palacios JM, Hoyer D (1989b) 5-HT1D receptors in guinea-pig and pigeon brain. Radioligand binding and biochemical studies. Naunyn-Schmiedeberg's Arch Pharmacol 340:486–494

    Google Scholar 

  • Waeber C, Palacios JM (1991) 5-HT1C, 5-HT1D and 5-HT2 receptors in mammalian brain: multiple affinity states with a different regional distribution. In: Fozard JR, Saxena PR (eds) Serotonin: molecular biology receptors and functional effects. Birkhäuser, Basel, pp 107–116

    Google Scholar 

  • Waeber C, Palacios JM (1992) Non 5-HT1A/5-HT1C [3H]5-HT binding sites in the hamster, opossum and rabbit brain show similar regional distribution but different sensitivity to beta-adrenoceptor antagonists. Synapse 12:261–270

    Google Scholar 

  • Zgombick JM, Schoeffter LE, Kucharewicz S, Weinshank RL, Hartig PR, Branchek TA (1994) The 5-HT2 antagonists ketanserin and ritanserin discriminate between recombinant human 5-HT1Dα, and 5-HT1D\ receptor subtypes: identification of selective 5-HT1Dα antagonists. Soc Neurosci Abstr 20:6337

    Google Scholar 

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  1. Stroke and Neurovascular Regulation, Massachusetts General Hospital, Neurosurgery Service, Department of Surgery, Neurology Service, Harvard Medical School CNY149 6403, 149 13th Street, 02129, Charlestown, MA, USA

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Waeber, C., Moskowitz, M. [3H]sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic study. Naunyn-Schmiedeberg's Arch Pharmacol 352, 263–275 (1995). https://doi.org/10.1007/BF00168556

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