5-Hydroxytryptamine3 receptors sited on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release.
Synaptosomes prepared from freshly obtained human cerebral cortex and labeled with [3H]choline have been used to investigate the modulation of [3H]acetylcholine ([3H]ACh) release by 5-hydroxytryptamine (5-HT). The Ca(2+)-dependent release of [3H]-ACh occurring when synaptosomes were exposed in superfusion to 15 mM KCl was inhibited by 5-HT (0.01-1 microM) in a concentration-dependent manner. The effect of 5-HT was mimicked by 1-phenylbiguanide, a 5-HT3 receptor agonist, but not by 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT1A receptor agonist. The 5-HT3 receptor antagonists tropisetron and ondansetron blocked the effect of 5-HT, whereas spiperone and ketanserin were ineffective. It is suggested that cholinergic axon terminals in the human cerebral cortex possess 5-HT receptors that mediate inhibition of ACh release and appear to belong to the 5-HT3 type.
Maura
G
G
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Andrioli
G C
GC
Cavazzani
P
P
Raiteri
M
M
D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D001369:Axons / Q000737:chemistry / Q000648:ultrastructure*; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D002794:Choline; D002799:Cholinergic Fibers / Q000737:chemistry / Q000648:ultrastructure*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017294:Ondansetron; D011985:Receptors, Serotonin / Q000032:analysis* / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014316:Tritium; D000077526:Tropisetron
D007093:Imidazoles; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014316:Tritium; D012701:Serotonin; D017294:Ondansetron; D000077526:Tropisetron; D002794:Choline; D000109:Acetylcholine; D002118:Calcium