POTENTIATION OF 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION IN RAT AORTA BY CHLORPHENIRAMINE, CITALOPRAM AND FLUOXETINE

This study examined the effects of chlorpheniramine, citalopram and fluoxetine on 5-hydroxytryptamine (5-HT)-induced contraction and 5-HT uptake in rat thoracic aortic rings in vitro. Chlorpheniramine and citalopram markedly potentiated 5-HT-induced contraction. Potentiation by fluoxetine was less pronounced. Chlorpheniramine (0.01-1-mu-M) and citalopram (0.1-1-mu-M) induced concentration-dependent parallel shifts to the left of the 5-HT concentration-response curves. The potentiation by chlorpheniramine was selective as chlorpheniramine (1-mu-M) did not potentiate phenylephrine-induced contraction. The potentiation did not depend upon the presence of endothelium, and was not related to H-1 receptor antagonism as diphenhydramine and pyrilamine (1-mu-M) did not similarly enhance 5-HT-induced contractions. Whereas cocaine (1-10-mu-M) similarly potentiated 5-HT-induced contraction, imipramine (1-10-mu-M) inhibited, rather than enhanced, contraction elicited by 5-HT. In the presence of 10-mu-M cocaine, maximally effective concentrations of chlorpheniramine (1-mu-M) or citalopram (100 nM) did not induce any additional potentiation of 5-HT-induced contraction. Cooling (4-degrees-C) markedly inhibited uptake of [H-3]5-HT in rings with and without endothelium. Although less marked, imipramine (10-mu-M), cocaine (1-mu-M), chlorpheniramine (1-mu-M) and citalopram (100 nM) inhibited [H-3]5-HT uptake in endothelium-intact and endothelium-denuded rings. Fluoxetine also inhibited [H-3]5-HT uptake, but the inhibition was only statistically significant in endothelium-intact rings. The monoamine oxidase (MAO) inhibitor, pargyline (10-100-mu-M), did not significantly affect 5-HT-induced contraction. The results demonstrate that chlorpheniramine, citalopram and to a lesser extent, fluoxetine potentiate 5-HT-induced contraction in rat aorta in which neuronal 5-HT uptake is negligible. The data are consistent with inhibition of non-neuronal 5-HT uptake as at least one mechanism responsible for potentiation of 5-HT-induced contraction in rat aorta by chlorpheniramine, citalopram and fluoxetine.