CCK-mediated response in the activation of 5-HT receptor types in the guinea-pig ileum

The possible interaction between cholecystokinin (CCK) and 5-hydroxytryptam ine (5-HT) was evaluated in vitro in the longitudinal muscle-myenteric plex us of the guinea-pig ileum. Devazepide and L-365,260 were used to block CCK A and CCKB receptors and ondansetron and tropisetron to block 5-HT3 and 5-H T4 receptors, respectively. The CCK receptor antagonists blocked, in a dose -dependent manner, the response to 5-HT and to the selective agonists at 5- HT3 and 5-HT4 receptors, 2-methyl-5-hydroxytryptamine (2-Me-5-HT) and 5-met hoxytryptamine (5-MeOT), respectively. The blockade was almost complete on the first phase of the concentration response curve to 5-HT and for all the concentrations of 5-MeOT tested. In. the 2-Me-5-HT-induced contractile res ponse there was a component with the same sensitivity to devazepide and to the selective NK1 receptor antagonist; GR 82334, and another resistant comp onent that was abolished by atropine. However, the blockade of the NK1 rece ptor did not produce a significant increase in the inhibition obtained when atropine or devazepide were separately tested, on the 5-MeOT-induced respo nse. These results suggest that CCK is involved in the 5-HT-induced contrac tile response, particularly in the response induced by 5-HT4 receptor stimu lation.