Extracellular 5-hydroxytryptamine inhibits 5-hydroxytryptamine release from rat brain cortex slices.
Rat brain cortex slices preincubated with 3H-5-hydroxytryptamine were superfused with physiological salt solution and stimulated electrically, or they were superfused with Ca2+-free solution containing 25 mM K+ and stimulated by introduction of 1.3 mM CaCl2 for 2 min. After blockade of neuronal 5-hydroxy-tryptamine (5-HT) uptake with clomipramine or paroxetine, the 3H overflow evoked by both methods of stimulation was decreased by unlabelled 5-HT and increased by methiothepin. The inhibition caused by 5-HT was antagonized by simultaneous administration of methiothepin. The inhibition by 5-HT of Ca2+-induced overflow was also observed in the presence of tetrodotoxin. These results suggest that 5-HT regulates its own release from central serotoninergic neurones by activating presynaptic 5-HT autoreceptors, thus decreasing the availability of Ca2+ for stimulus-release coupling.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002997:Clomipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D012701:Serotonin; D013779:Tetrodotoxin; D008719:Methiothepin; D002997:Clomipramine; D002118:Calcium