Skip to main content
Log in

Serotonin autoreceptor in rat hippocampus: Pharmacological characterization as a subtype of the 5-HT1 receptor

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The 5-hydroxytryptamine (5-HT) autoreceptors mediating inhibition of [3H]5-HT release in rat hippocampus have been characterized pharmacologically in terms of 5-HT receptor subtype by using superfused synaptosomes depolarized with 15 mM KCl. Exogenous 5-HT inhibited in a concentration-dependent way (pEC30=8.74) the K+-evoked release of [3H]5-HT. Methiothepin shifted the concentration-response curve of 5-HT to the right (pA2=8.62). The 5-HT2 receptor antagonists, ketanserin, methysergide or spiperone were ineffective against 5-HT. The 5-HT1 receptor agonist, 5-methoxy-3-[1,2,3,6-tetra-hydropyridin-4-yl]-1H-indole (RU 24969) mimicked 5-HT and was equipotent as an inhibitor of the release of [3H]5-HT. In contrast, the putative 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was almost ineffective at 1 μM. Finally, (−)propranolol, used as a non-selective 5-HT1A/5-HT1B receptor antagonist, shifted to the right (pA2=7.91) the concentration-response curve of 5-HT whereas the 5-HT1C receptor antagonist mesulergine was ineffective. In conclusion, 5-HT nerve terminals of rat hippocampus possess autoreceptors which appear to belong to the 5-HT1B subtype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 317:36–43

    Google Scholar 

  • Bonanno G, Maura G, Raiteri M (1986) Pharmacological characterization of release-regulating serotonin autoreceptors in rat cerebellum. Eur J Pharmacol 126:317–321

    Google Scholar 

  • Bradford MM (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Google Scholar 

  • Cerrito F, Raiteri M (1979) Serotonin release is modulated by presynaptic autoreceptors. Eur J Pharmacol 57:427–430

    Google Scholar 

  • de Montigny C (1984) Electroconvulsive shock treatments enhance responsiveness of forebrain neurons to serotinin. J Pharmacol Exp Ther 228:230–234

    Google Scholar 

  • Doods HN, Kalkman HO, de Jonge A, Thoolen MJMC, Wilffert B, Timmermans PBMWM, Van Zwieten PA (1985) Differential selectivities of RU 24969 and 8-OH-DPAT for the purported 5-HT1A and 5-HT1B binding sites. Correlation between 5-HT1A affinity and hypotensive activity. Eur J Pharmacol 112:363–370

    Google Scholar 

  • 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

    Google Scholar 

  • Euvrard C, Boissier JR (1980) Biochemical assessment of the central 5-HT agonist activity of RU 24969 (a piperidinyl indole). Eur J Pharmacol 63:65–72

    Google Scholar 

  • Furchgott RF (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Handbook of experimental pharmacology. Catecholamines, vol XXXIII. Springer, Berlin Heidelberg New York, pp 283–335

    Google Scholar 

  • Göthert M, Weinheimer G (1979) Extracellular 5-hydroxytryptamine inhibit 5-hydroxytryptamine release from rat brain cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 310:93–96

    Google Scholar 

  • Gozlan H, El Mestikawy S, Pichat L, Glowinski J, Hamon M (1983) Identification of presynaptic serotonin autoreceptors using a new ligand:3H-PAT. Nature 305:140–142

    Google Scholar 

  • Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron microscopic study of cell fragments derived by homogenization and centrifugation. J Anat 96:79–87

    Google Scholar 

  • Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikstrom H, Arvidson LE, Hacksell U, Nilsson JLG (1982) 8-Hydroxy-2-(di-n-propylamino)tetraline, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT receptor stimulating activity. J Neural Transm 55:169–188

    Google Scholar 

  • 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

    Google Scholar 

  • Leysen JE, Niemegeers CJE, Van Nueten JM and Laduron PM (1982)3H-ketanserin (R 41468), a selective3H-ligand for serotonin2 receptor binding sites. Molec Pharmacol 21:301–314

    Google Scholar 

  • Martin LL, Sanders-Bush E (1982) 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 

  • Middlemiss DN (1984a) Stereoselective 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, Fozard JR (1983) 8-hydroxy-2-(di-n-propyl-amino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol 90:151–153

    Google Scholar 

  • Monroe PJ, Smith DJ (1985) Demonstrations of an autoreceptor modulating the release of [3H]5-hydroxytryptamine from a synaptosomal-rich spinal cord tissue preparation. J Neurochem 45:1886–1894

    Google Scholar 

  • Pazos A, Hoyer D, Palacios JM (1984) 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 

  • Pedigo NW, Yamamura HJ, Nelson DL (1981) Discrimination of multiple3H-5-hydroxytryptamine binding sites by the neuroleptic spiperone in rat brain. J Neurochem 36:220–226

    Google Scholar 

  • Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethyl amide and [3H]spiroperidol. Molec Pharmacol 16:687–699

    Google Scholar 

  • Raiteri M, Angelini F, Levi G (1974) A simple apparatus for studying the release of neurotransmitters from synaptosomes. Eur J Pharmacol 25:411–414

    Google Scholar 

  • Raiteri M, Maura G, Versace P (1983a) Functional evidence for two stereochemically different alpha-2 adrenoceptors regulating central norepinephrine and serotonin release. J Pharmacol Exp Ther 224:679–685

    Google Scholar 

  • Raiteri M, Maura G, Gemignani A, Pittaluga A (1983b) Differential blockade by (−)mianserin of the alpha2-adrenoceptors mediating inhibition of noradrenaline and serotonin release from rat brain synaptosomes. Naunyn-Schmiedeberg's Arch Pharmacol 322:180–182

    Google Scholar 

  • Stauderman KA, Jones DJ (1986) Presynaptic serotonin receptors regulate [3H]serotonin release from rat spinal cord synaptosomes. Eur J Pharmacol 120:107–109

    Google Scholar 

  • Verge D, Daval G, Patey A, Gozlan H, El Mestikawy S, Hamon M (1985) Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur J Pharmacol 113:463–464

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maura, G., Roccatagliata, E. & Raiteri, M. Serotonin autoreceptor in rat hippocampus: Pharmacological characterization as a subtype of the 5-HT1 receptor. Naunyn-Schmiedeberg's Arch. Pharmacol. 334, 323–326 (1986). https://doi.org/10.1007/BF00569364

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00569364

Key words

Navigation