Serotonin autoreceptor in rat hippocampus: pharmacological characterization as a subtype of the 5-HT1 receptor.
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-tetrahydropyridin-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 microM. 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.
D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists