Effects of L-type Ca2+ channel blockers on 5- hydroxytryptamine (5-HT) release from isolated mouse intestinal tissues

The release of 5-HT from enterochromaffin (EC) cells seems to occur via exocytosis depending on intracellular Ca2+ concentration. In this study, we investigated the effect of various L-type Ca2+ channel blockers on 5-HT release from isolated mouse intestinal mucosa. 5-HT release was increased depending on the increasing concentration of extracellular Ca2+. fluvoxamine, a selective serotonin re- uptake inhibitor, additively increased the rise of 5-HT release induced by Ca2+. The high extracellular Ca2+ (5. 0 mM)-induced 5-HT increase was significantly inhibited by HIA1164 (10-6 M), a new Ca2+ channel blocker. Diltiazem (10-6 M) or nicardipine (10-6 M) tended to decrease the 5- HT increase induced by 5. 0mM Ca2+. 2-Methyl-5-HT, a selective 5-HT3 receptor agonist-induced increase in 5-HT release was significantly inhibited by HIA1164 (10-6 M) and diltiazem (10-5 M). Both HIA1164 (10-6 M) and diltiazem (10-6 M) could not inhibit 5-HT increase by 5- methoxytryptamine, a selective 5-HT4 receptor agonist. Cyclophosphaniide-induced 5-HT release was inhibited by HIA1164 (10-6 M). These results suggest that voltage- dependent L-type Ca2+ channels are involved in 5-HT release induced by 5-HT3 receptors stimulation, but not by G protein-coupled 5-HT4 receptors stimulation in mouse intestinal mucosa.