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An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney

Apparent distinction from the 5-HT1A, 5-HT1B and 5-HT1C subtypes

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Summary

The present study has identified a receptor for 5-hydroxytryptamine (5-HT) which functions to inhibit the stimulus-induced release of [3H] noradrenaline following sympathetic periarterial nerve stimulation to the isolated perfused rat kidney. In addition to 5-HT (IC30=4.5×10−8 mol/l), both 5-carboxamidotryptamine (IC30=8×10−9 mol/l) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl) indole (RU-24969, IC30=2.5×10−7 mol/l) acted as agonists whereas 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was inactive. The inhibitory effect of 5-HT on the electrically-evoked release of tritium was antagonized in a concentration-dependent manner by methiothepin (IC50=4×10−9 mol/l), metergoline (IC50=4×10−8 mol/l) and methysergide (IC50=1.3×10−7 mol/l) but not by cyproheptadine, ketanserin, mesulergine, (−)-propranolol, (±)-pindolol, (±)-cyanopindolol, metoclopramide or phentolamine. It is concluded that the receptor to 5-HT conforms to general criteria defining 5-HT1-like receptors but at the present time the receptor site cannot be fitted to the designated 5-HT1A, 5-HT1B or 5-HT1C subtypes.

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References

  • Adler-Graschinsky E (1983) Dual presynaptic effects of 5-hydroxytryptamine on peripheral noradrenergic synapses. J Auton Pharmacol 3:303–315

    Google Scholar 

  • Asarch KB, Ransom RW, Shih JC (1985) 5-HT-1a and 5-HT-1b selectivity of the two phenylpiperazine derivatives: Evidence for 5-HT-1b heterogeneity. Life Sci 36:1265–1273

    Google Scholar 

  • Baumann PA, Waldmeier PC (1982) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 317:36–43

    Google Scholar 

  • Charlton KG, Johnson TD, Clarke DE (1984) Vasoconstrictor and norepinephrine potentiating action of 5-hydroxykynuramine in the isolated perfused rat kidney: Involvement of serotonin receptors and alpha1-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 328:154–159

    Google Scholar 

  • Cohen ML (1984) Vascular serotonin receptors and blood pressure regulation. Drug Develop Res 4:301–313

    Google Scholar 

  • Connor HE, Feniuk W, Humphrey PPA, Perren MJ (1985) 5-Carboxamido-tryptamine is a selective agonist at 5-HT receptors mediating vasodilation and tachycardia in the anaesthetised cat. Br J Pharmacol 85:222P

  • Cortés E, Palacios JM, Pazos A (1984) Visualization of multiple serotonin receptors in the rat brain by autoradiography. Br J Pharmacol 82:202P

    Google Scholar 

  • Doxey JC, Roach AG, Smith CFC (1983) Studies on RX781094: A selective, potent and specific antagonist of α2-adrenoceptors. Br J Pharmacol 78:489–505

    Google Scholar 

  • Ekas RD, Steenberg ML, Woods MS, Lokhandwala MF (1983) Presynaptic α- and β-adrenoceptor stimulation and norepinephrine release in the spontaneously hypertensive rat. Hypertension 5:198–204

    Google Scholar 

  • Engel G, Göthert M, Müller-Schweinitzer E, Schlicker E, Sistonen L, Stadler PA (1983) Evidence for common pharmacological properties of [3H]-5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves. Naunyn-Schmiedeberg's Arch Pharmacol 324:116–124

    Google Scholar 

  • Feniuk W (1984) An analysis of 5-hydroxytryptamine receptors mediating contraction of isolated smooth muscle. Neuropharmacology 23:1467–1472

    Google Scholar 

  • Feniuk W, Humphrey PPA, Watts AD (1979) Presynaptic inhibitory action of 5-hydroxytryptamine in dog isolated saphenous vein. Br J Pharmacol 67:247–254

    Google Scholar 

  • Feniuk W, Humphrey PPA, Watts AD (1981a) Further characterization of pre- and post-junctional receptors for 5-hydroxytryptamine in isolated vasculature. Br J Pharmacol 73:191P-192P

    Google Scholar 

  • Feniuk W, Humphrey PPA, Watts AD (1981b) Modification of the vasomotor actions of methysergide in the femoral bed of the anesthetized dog by changes in the sympathetic nerve activity. J Auton Pharmacol 1:127–132

    Google Scholar 

  • Fozard JR (1983) Functional correlates of 5-HT1 recognition sites. Trends Pharmacol Sci 4:288–289

    Google Scholar 

  • Fozard JR (1984) Neuronal 5-HT receptors in the periphery. Neuropharmacology 23:1473–1486

    Google Scholar 

  • Gaddum JH, Picarelli ZP (1957) Two kinds of tryptamine receptor. Br J Pharmacol 12:323–328

    Google Scholar 

  • Göthert M, Schlicker E (1983) Autoreceptor-mediated inhibition of3H-5-hydroxytryptamine release from rat brain cortex slices by analogues of 5-hydroxytryptamine. Life Sci 32:1183–1191

    Google Scholar 

  • Göthert M, Kollecker P (1985) Presynaptic 5-hydroxytryptamine1 (5-HT1) receptors on the sympathetic nerves of the human saphenous vein. Naunyn-Schmiedeberg's Arch Pharmacol 329:R83

    Google Scholar 

  • Gradin K, Petterson A, Hjorth S, Hedner T, Arvidsson LE, Persson B (1985) Cardiovascular effects in the Sprague-Dawley rat of 8-hydroxy-2(di-N-propylamino) tetralin, a selective 5-hydroxytryptamine receptor agonist. J Pharma Pharmacol 37: 263–265

    Google Scholar 

  • Hoyer D (1985) Characterization of multiple serotonin (5-HT) recognition sites in rat and pig brain membranes by radioligand binding. Naunyn-Schmiedeberg's Arch Pharmacol 329:R82

    Google Scholar 

  • Humphrey PPA (1984) Peripheral 5-hydroxytryptamine receptors and their classification. Neuropharmacology 23:1503–1510

    Google Scholar 

  • Humphrey PPA, Feniuk W, Watts AD (1983) Prejunctional effects of 5-hydroxytryptamine on noradrenergic nerves in the cardiovascular system. Fed Proc 42:218–222

    Google Scholar 

  • Kalkman HO, Boddeke HWGM, Doods HN, Timmermans PBMWM, van Zwieten PA (1983) Hypotensive activity of serotonin receptor agonists in rats is related to their affinity for 5-HT1 receptors. Eur J Pharmacol 91:155–156

    Google Scholar 

  • Kapur H, Mottram DR (1979) A pre-synaptic inhibitory effect of 5-hydroxytryptamine on the electrically induced twitch response of the rat vas deferens. Biochem Pharmacol 28:951–952

    Google Scholar 

  • Kawasaki H, Takasaki K (1984) Vasoconstrictor response induced by 5-hydroxytryptamine released from vascular adrenergic nerves by periarterial nerve stimulation. J Pharmacol Exp Ther 229:816–822

    Google Scholar 

  • Kimura T, Satoh S (1983) Presynaptic inhibition by serotonin of cardiac sympathetic transmission in dogs. Clin Exp Pharmacol Physiol 10:535–542

    Google Scholar 

  • Lawang A, Saxena PR (1985) Pharmacological comparison between 5-hydroxytryptamine (5-HT) and 5-carboxamide tryptamine (5-CT). Br J Pharmacol 85: 316P

  • Leysen J (1983) Serotonin receptor binding sites: Is there pharmacological and clinical significance? Med Biol 61:139–143

    Google Scholar 

  • Leysen J (1984) Problems inin vitro receptor binding studies and identification and role of serotonin receptor sites. Neuropharmacology 23:247–254

    Google Scholar 

  • Leysen JE (1985) Serotonin binding sites. In: Vanhoutte PM (ed) Serotonin and the cardiovascular system. Raven Press, New York, pp 43–62

    Google Scholar 

  • Leysen JE, Tollenaere JP (1982) Biochemical models for serotonin receptors. Annual Reports Med Chem 17:1–10

    Google Scholar 

  • Martin LL, Sanders-Bush E (1982a) Comparison of the pharmacological characteristics of 5-HT1 and 5-HT2 binding sites with those of serotonin autoreceptors which modulate serotonin release. Naunyn-Schmiedeberg's Arch Pharmacol 321:165–170

    Google Scholar 

  • Martin LL, Sanders-Bush E (1982b) The serotonin autoreceptor: Antagonism by quipazine. Neuropharmacology 21:445–450

    Google Scholar 

  • Martinez AA, Lokhandwala MF (1980) Evidence for a presynaptic inhibitory action of 5-hydroxytryptamine on sympathetic neurotransmission to the myocardium. Eur J Pharmacol 63:303–311

    Google Scholar 

  • Middlemiss DN (1982) Multiple 5-hydroxytryptamine receptors in the central nervous system of the rat. In: Belleroche JD (ed) Presynaptic receptors: mechanism and function. Ellis Harwood Ltd, Chichester, pp 46–74

    Google Scholar 

  • Middlemiss DN (1984a) Stereospecific blockade at [3H]5-HT binding sites and at the 5-HT autoreceptor by propranolol. Eur J Pharmacol 101:289–293

    Google Scholar 

  • Middlemiss DN (1984b) 8-Hydroxy-2-(di-n-propylamino) tetralin is devoid of activity at the 5-hydroxytryptamine autoreceptor in rat brain. Implications for the proposed link between the autoreceptor and the [3H] 5-HT recognition site. Naunyn-Schmiedeberg's Arch Pharmacol 327:18–22

    Google Scholar 

  • Middlemiss DN (1984c) RU-24969 inhibits K+-evoked release of [3H]-5-HT from rat frontal cortex slices via stimulation of the 5-HT autoreceptor. 14th CINP Congr Florence 657P

  • Middlemiss DN, Fozard JR (1983) 8-Hydroxy-2-(DI-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol 90:151–153

    Google Scholar 

  • Middlemiss DN, Neill J, Tricklebank MD (1985) Subtypes of the 5-HT receptor involved in hypothermia and forepaw treading induced by 8-OH-DPAT. Proc Br Pharmacol Soc Cardiff

  • Nahorski SR, Willcocks AL (1983) Interactions of β-adrenoceptor antagonists with 5-hydroxytryptamine receptor subtypes in rat cerebral cortex. Br J Pharmacol 78:107P

    Google Scholar 

  • Pazos A, Hoyer D, Palacios JM (1984a) The binding of serotonergic ligands to the porcine choroid plexus: Characterization of a new type of serotonin recognition site. Eur J Pharmacol 106:539–546

    Google Scholar 

  • Pazos A, Hoyer D, Palacios JM (1984b) Mesulergine, a selective serotonin-2 ligand in the rat cortex, does not label these receptors in porcine and human cortex: Evidence for species differences in brain serotonin-2 receptors. Eur J Pharmacol 106:531–538

    Google Scholar 

  • 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

    Google Scholar 

  • Peroutka SJ (1984) Vascular serotonin receptors: Correlation with 5-HT1 and 5-HT2 binding sites. Biochem Pharmacol 33:2349–2353

    Google Scholar 

  • Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: Differential binding of [3H]lysergic acid diethylamide and [3H] spiroperidol. Mol Pharmacol 16:687–699

    Google Scholar 

  • Peroutka SJ, Lebovitz RM, Snyder SH (1981) Two distinct central serotonin receptors with different physiological functions. Science 212:827–829

    Google Scholar 

  • Petrovic T, Bell C (1984) Small fluorescent cells in the rat kidney contain 5-hydroxytryptamine not a catecholamine. J Auton Nervous System 11:329–338

    Google Scholar 

  • Saxena PR, Verdouw PD (1985) 5-Carboxamide tryptamine, a compound with high affinity for 5-hydroxytryptamine1 binding sites, dilates arterioles and constricts arteriovenous anastomoses. Br J Pharmacol 84:533–544

    Google Scholar 

  • Saxena PR, Mylecharane EJ, Heiligers J (1985) Analysis of the heart rate effects of 5-hydroxytryptamine in the cat: Mediation of tachycardia by 5-HT-like receptors. Naunyn-Schmiedeberg's Arch Pharmacol 330:121–129

    Google Scholar 

  • Schlicker E, Hillenbrand K (1985) Antagonistic properties of β-adrenoceptor antagonists at presynaptic serotonin autoreceptors in the rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 329:R83

    Google Scholar 

  • Schurek HJ, Brecht JP, Lohfert H, Hierholzer K (1975) The basic requirements for the function of the isolated cell free perfused rat kidney. Pflügers Arch 359:349–365

    Google Scholar 

  • Sills MA, Wolfe BB, Frazer A (1984) Determination of selective and nonselective compounds for the 5-HT1A and 5-HT1B receptor subtypes in rat frontal cortex. J Pharmacol Exp Ther 231:480–487

    Google Scholar 

  • Stier CT, McKendall G, Itskovitz HD (1984) Serotonin formation in nonblood-perfused kidneys. J Pharmacol Exp Ther 228:53–56

    Google Scholar 

  • Timmermans PBMWM, Mathy M-J, Wilfert B, Kalkman HO, Smit G, Dijkstra D, Horn AS, van Zwieten PA (1984) 15-1 agonist selectivity of mono- and dihydroxy-2-N,N-di-n-propylaminotetralins. Eur J Pharmacol 97:55–65

    Google Scholar 

  • Tricklebank MD, Forler C, Fozard JR (1984) The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(DL-n-propylamino) tetralin in the rat. Eur J Pharmacol 106:271–282

    Google Scholar 

  • Verbeuren TJ, Jordaens FH, Herman AG (1983) Accumulation and release of [3H]-5-hydroxytryptamine in saphenous veins and cerebral arteries of the dog. J Pharmacol Exp Ther 226:579–588

    Google Scholar 

  • Wallis D (1981) Neuronal 5-hydroxytryptamine receptors outside the central nervous system. Life Sci 29:2345–2355

    Google Scholar 

  • Watts AD, Feniuk W, Humphrey PPA (1981) A pre-junctional action of 5-hydroxytryptamine and methysergide on noradrenergic nerves in dog isolated saphenous vein. J Pharm Pharmacol 33:515–520

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, University of Houston-University Park, 77004, Houston, Texas, USA

    K. G. Charlton, R. A. Bond & D. E. Clarke

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  1. K. G. Charlton
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  2. R. A. Bond
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  3. D. E. Clarke
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Additional information

Preliminary accounts of this work were presented to the British Pharmacological Society in London (December, 1984) and Southampton (July, 1985)

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Charlton, K.G., Bond, R.A. & Clarke, D.E. An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 8–15 (1986). https://doi.org/10.1007/BF00633190

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  • DOI: https://doi.org/10.1007/BF00633190

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