Autoreceptor-mediated inhibition of 3H-5-hydroxytryptamine release from rat brain cortex slices by analogues of 5-hydroxytryptamine.
Rat brain cortex slices preincubated with 3H-5-hydroxytryptamine (3H-5-HT) were superfused with physiological salt solution containing paroxetine, an inhibitor of 5-hydroxytryptamine (5-HT) uptake. The effects of various indolethylamines on the electrically evoked tritium overflow (containing 66.3% unmetabolized 3H-5-HT) were investigated (the percentage of unmetabolized 3H-5-HT was not altered by the indolethylamines or metitepin). 6,7-Dihydroxytryptamine (6,7-DHT) did not affect the stimulation-evoked tritium overflow, whereas the latter was inhibited by the other tryptamine derivatives investigated; when the compounds were compared to each other on the basis of their inhibitory potencies the following rank order was obtained: unlabelled 5-HT greater than 5-methoxytryptamine greater than 4-HT greater than 6-HT greater than 5,6-DHT greater than tryptamine greater than 7-HT greater than 5,7-DHT. The inhibitory effects of these compounds were antagonized by metitepin. It is concluded that the indolethylamines inhibit the stimulation-evoked 3H-5-HT release by activating the presynaptic 5-HT autoreceptors on the 5-HT neurones of the rat brain cortex. Similarities may exist between these receptors and the postsynaptic 5-HT1 binding sites of this brain area.
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D004102:Dihydroxytryptamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000494:pharmacology*
D004102:Dihydroxytryptamines; D011985:Receptors, Serotonin; D014363:Tryptamines; D012701:Serotonin; D008735:5-Methoxytryptamine; D008719:Methiothepin