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

The possible interaction between cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT) was evaluated in vitro in the longitudinal muscle-myenteric plexus of the guinea-pig ileum. Devazepide and L-365,260 were used to block CCKA and CCK(B) receptors and ondansetron and tropisetron to block 5-HT3 and 5-HT4 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-methoxytryptamine (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 response there was a component with the same sensitivity to devazepide and to the selective NK1 receptor antagonist, GR 82334, and another resistant component that was abolished by atropine. However, the blockade of the NK1 receptor did not produce a significant increase in the inhibition obtained when atropine or devazepide were separately tested on the 5-MeOT-induced response. These results suggest that CCK is involved in the 5-HT-induced contractile response, particularly in the response induced by 5-HT4 receptor stimulation.