Uptake and release of 5-hydroxytryptamine by enteric 5-hydroxytryptaminergic neurones: effects of fluoxetine (Lilly 110140) and chlorimipramine.
The effect of fluoxetine on uptake of 5-hydroxytryptamine (5-HT) by enteric 5-hydroxytryptaminergic neurones has been analyzed in order to compare further these neurones with 5-HT neurones of the CNS. In addition, the effects of fluoxetine and chlorimipramine on efflux of [3H]-5-HT from the myenteric plexus were also evaluated. Fluoxetine was found to be a competitive inhibitor of 5-HT uptake by the myenteric plexus and was a more potent inhibitor of 5-HT uptake than was chlorimipramine. However, chlorimipramine enhanced the efflux of [3H]-5-HT more than could be explained by inhibition of 5-HT uptake and, therefore, appears to have the additional action of releasing the amine. These observations, similar to those of others studying central neurones, support the view that enteric 5-HT neurones resemble those of the CNS and are a useful model for the evaluation of drugs.
D000818:Animals; D002997:Clomipramine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D006168:Guinea Pigs; D006207:Half-Life; D007700:Kinetics; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*
D003984:Dibenzazepines; D011437:Propylamines; D005473:Fluoxetine; D012701:Serotonin; D002997:Clomipramine