The serotonin (5-HT) autoreceptor in the hippocampus of the rabbit: role of 5-HT biophase concentration.
Slices of hippocampus from the rabbit were preincubated with [3H]5-HT), then superfused continuously and twice stimulated electrically. The stimulation-evoked overflow of tritium was inhibited by the 5-HT autoreceptor ligands 5-carboxamido-tryptamine (5-COHT), 5-HT, 5-methoxy-N,N-dimethyl-tryptamine (5-MeOMT), (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), methysergide and (+/-)-cyanopindolol in a concentration-dependent manner. These effects were competitively inhibited by the 5-HT autoreceptor antagonists, metitepin and metergoline. (+/-)-Cyanopindolol also reduced the evoked release of 5-HT from slices of cortex from the rat. The inhibitor of the uptake of 5-HT, 6-nitroquipazine diminished the autoreceptor-mediated depression of release of 5-HT. In cortex tissue from the rat, 6-nitroquipazine reversed the decreased release of 5-HT, due to (+/-)-cyanopindolol, to a facilitation. The disinhibition of the release of 5-HT by autoreceptor antagonists was further enhanced by 6-nitroquipazine. Non-linear regression analysis of concentration-response curves for 5-COHT yielded the following pKd of endogenous 5-HT at the autoreceptor: 7.753 +/- 0.116. This value corresponds to the pKd of 5-HT at the 5-HT1B binding site. The 5-HT biophase concentration at the autoreceptor of 10(-8.220 +/- 0.132)M was markedly enhanced by 6-nitroquipazine (10(-6)M) to 10(-7.476 +/- 0.132)M. It is concluded that the 5-HT autoreceptor belongs to the 5-HT1B subtype of receptor; the corresponding 5-HT biophase concentration can be estimated quantitatively; 8-OH-DPAT decreased the evoked release of 5-HT through both 5-HT autoreceptors and alpha 2-heteroreceptors and (+/-)-cyanopindolol acts as partial agonist at the 5-HT autoreceptor.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000378:metabolism*; D008433:Mathematics; D008711:Metergoline / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D008732:Methoxydimethyltryptamines / Q000378:metabolism; D008784:Methysergide / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011814:Quipazine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D008732:Methoxydimethyltryptamines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D008711:Metergoline; D012701:Serotonin; C047975:cyanopindolol; D011814:Quipazine; D008719:Methiothepin; C031227:6-nitroquipazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D010869:Pindolol; D008784:Methysergide; D010646:Phentolamine