Summary
1) 5-HT (5-hydroxytryptamine, serotonin) induces inositol phosphate production in a pig choroid plexus preparation. This effect has been pharmacologically characterized and the data compared to those obtained from radioligand binding studies performed with [3H]mesulergine to 5-HT1C sites in pig choroid plexus membranes. 2) The rank order of potency of agonists stimulating inositol phosphate production was: α-methyl-5-HT > 1-methyl-5-HT > DOI > bufotenine = SKF 83566 = 5-HT > 5-MeO-DMT > 5-MeOT = RU 24969> SCH 23390> 5-CT. 8-OH-DPAT was virtually devoid of activity at 100 μmol/l. 3) The increase in inositol phosphate production induced by 5-HT and other agonists was surmountably antagonised by mesulergine, ketanserin and spiperone with pKB values of 8.7, 6.7 and 5.3, respectively. 4) The rank order of potency of antagonists was: metergoline > mesulergine > LY 53857 > ritanserin > methiothepin > mianserin > cyproheptadine > pirenperone > cinanserin > ketanserin > spiperone. The following antagonists were virtually devoid of activity at 100 μmol/l; pindolol, 21-009 and yohimbine. 5) The results obtained both with agonists and antagonists strongly support the view that 5-HT1C receptors mediate agonist induced production of inositol phosphates in pig choroid plexus. This is illustrated by the close similarity between 5-HT1C binding and stimulation of inositol phospholipid turnover in this preparation. 6) The present data also show that compounds believed to be selective for dopamine D1 receptors (SKF 83566, SCH 23390) or 5-HT2 receptors (DOI, α-methyl-5-HT, LY 53857, ritanserin, cyproheptadine) also interact with 5-HT1C receptors. 7) A case can be made for the 5-HT1C receptor, with its similarities to the 5-HT2 receptor in terms of pharmacology and second messenger coupling, being a 5-HT2 receptor subtype.
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References
Altar CA, Marien MR (1987) Picomolar affinity of 125I-SCH 23982 for D1 receptors in brain demonstrated with digital subtraction autoradiography. J Neurosci 7:213–222
Billard W, Ruperto V, Crosby G, Iorio LC, Barnett A (1984) Characterization of the binding of [3H]SCH 23390, a selective D-1 receptor antagonist ligand in rat striatum. Life Sci 35:1885–1893
Boyson SJ, McGonigle P, Molinoff, PB (1986) Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J Neurosci 6:3177–3188
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
Conn PJ, Sanders-Bush E (1986) Agonist-induced phosphoinositide hydrolysis in choroid plexus. J Neurochem 47:1754–1760
Conn PJ, Sanders-Bush E, Hoffman BJ, Hartig PR (1986) A unique serotonin receptor in choroid plexus is linked to phosphatidylinositol turnover. Proc Natl Acad Sci USA 83:4086–4088
De Lean A (1979) SCTFIT, A computer program for simultaneous analysis of saturation and competition curves. Howard Hughes Medical Institute, Duke University, Medical Center Durham, North Carolina
Doyle VM, Creba JA, Rüegg UT, Hoyer D (1986) Serotonin increases the production of inositol phosphates and mobilises calcium via the 5-HT2 receptor in A7r5 smooth muscle cells. Naunyn-Schmiedeberg's Arch Pharmacol 333:98–103
Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RJ (1988) The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 335:358–360
Frenken M, Kaumann AJ (1987) ICI 169,369 is both a competitive antagonist and an allosteric modulator of arterial 5-HT2 receptors (1987) Br J Pharmacol 91:350P
Glennon RA (1987) Central serotonin receptors as targets for drug research. J Med Chem 30:1–12
Hoyer D (1988a) Molecular pharmacology and biology of 5-HT1C receptors. TIPS 9:89–94
Hoyer D (1988b) Functional correlates to serotonin 5-HT1 recognition sites. J Rec Res 8:59–81
Hoyer D (1989) Biochemical mechanisms of 5-HT receptor-effector coupling in peripheral tissues. In: Fozard JR (ed) Peripheral actions of 5-HT. Oxford University Press, Oxford, pp 72–99
Hoyer D, Karpf A (1988) [125I]SCH 23982, a “selective” D1 receptor antagonist, labels with high affinity 5-HT1C sites in pig choroid plexus. Eur J Pharmacol 150:181–184
Hoyer D, Dravid A, Palacios JM (1987) Serotonin 5-HT1C receptor mediated hydrolysis of inositol lipids in pig choroid plexus. Naunyn-Schmiedeberg's Arch Pharmacol 335: (Suppl) R89
Hoyer D, Engel G, Kalkman HO (1985) Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (−) [125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin. Eur J Pharmacol 118:13–23
Hoyer D, Pazos A, Probst A, Palacios JM (1986a) Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res 376:97–197
Hoyer D, Srivatsa S, Pazos A, Engel G, Palacios JM (1986b) [125I]LSD labels 5-HT1C recognition sites in pig choroid plexus membranes: Comparison with [3H]mesulergine and [3H]5-HT binding. Neurosci Lett 69:269–274
Hoyer D, Waeber C, Pazos A, Probst A, Palacios JM (1988) Identification of a 5-HT1 recognition site in human brain membranes different from 5-HT1A 5-HT1B and 5-HT1C sites. Neurosci Lett 85:357–362
Hyttel J (1983) SCH 23390 the first selective dopamine D-1 antagonist. Eur J Pharmacol 91:153–154
Iorio LC, Barnett A, Leitz FH, Houser VP, Korduba CA (1983) SCH 23390, a potential benzodiazepine antipsychotic with unique interactions on dopaminergic systems. J Pharmacol Exp Ther 226:462–468
Julius D, MacDermott AB, Axel R, Jessel TM (1988) Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science 241:5558–5564
Kaumann AJ (1988) Allosteric effects of LSD and LY 53857 on the 5-HT2 receptor system of calf coronary artery. Naunyn-Schmiedeberg's Arch Pharmacol 337: R103
Kaumann A, Frenken M (1985) A paradox: the 5-HT2 receptor antagonist ketanserin restores the 5-HT-induced contraction depressed by methysergide in large coronary arteries of calf. Allosteric regulation of 5-HT2-receptors. Naunyn-Schmiedeberg's Arch Pharmacol 328:295–300
Kenakin T (1988) Are receptors promiscuous? Intrinsic efficacy as a transduction phenomenon. Life Sci 43:1095–1101
Lemoine H, Pohl V, Teng KJ (1988) Serotonin (5-HT) stimulates phosphatidylinositol (PI) hydrolysis only through the R-state of allosterically regulated 5-HT2 receptors in calf tracheal smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol 337: R103
Lyon RA, Davis KH, Titeler M (1987) 3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotidesensitive state of cortical 5-HT2 receptors. Mol Pharmacol 31:194–199
Markstein R, Hoyer D, Engel G (1986) 5-HT1A-receptors mediate stimulation of adenylate cyclase in rat hippocampus. Naunyn-Schmiedeberg's Arch Pharmacol 333:335–341
Palacios JM, Markstein R, Pazos A (1986) Serotonin-1 C sites in the choroid plexus are not linked in a stimulatory or inhibitory way to adenylate cyclase. Brain Res 380:151–154
Pazos A, Hoyer D, Palacios JM (1984a) Mesulergine, a selective serotonin-2 ligand in the rat cortex, does not label these receptors, in porcine and human cortex; evidence for species differences on brain serotonin-2 receptors. Eur J Pharmacol 106:531–538
Pazos A, Hoyer D, Palacios JM (1984b) The binding of serotonergic ligand to the porcine choroid plexus: characterization of a new type of serotonin recognition site. Eur J Pharmacol 106: 539–546
Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230
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, Snyder SH (1979) Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol 16:687–699
Pritchett DB, Bach AWJ, Wozny M, Taleb O, Dal Toso R, Shih J, Seeburg PH (1988) Structure and functional expression of cloned rat serotonin 5-HT2 receptor. EMBO J 7:4135–4140
Sidhu A, van Oene JC, Dandridge P, Kaiser C, Kebabian JW (1986) [125I]SCH 23982: the ligand of choice for identifying the D-1 dopamine receptor. Eur J Pharmacol 128:213–220
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These data have been presented in part at the Spring Meeting of the German Pharmacological Society, March 1987 (Hoyer et al. 1987)
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Hoyer, D., Waeber, C., Schoeffter, P. et al. 5-HT1C receptor-mediated stimulation of inositol phosphate production in pig choroid plexus. Naunyn-Schmiedeberg's Arch Pharmacol 339, 252–258 (1989). https://doi.org/10.1007/BF00173573
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DOI: https://doi.org/10.1007/BF00173573