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

Abstract:

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 CCK(A) and CCK(B) receptors and ondansetron and tropisetron to block 5-HT<inf>3</inf> and 5-HT<inf>4</inf> receptors, respectively. The CCK receptor antagonists blocked, in a dose-dependent manner, the response to 5-HT and to the selective agonists at 5-HT<inf>3</inf> and 5-HT<inf>4</inf> receptor, 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 NK<inf>1</inf> receptor antagonist, GR 82334, and another resistant component that was abolished by atropine. However, the blockade of the NK<inf>1</inf> receptor did not produce a significant increase in the inhibition obtained when atropine or devazepide were separately tested on the 5-Me-OT-induced response. These results suggest that CCK is involved in the 5-HT-induced contractile response, particularly in the response induced by 5-HT<inf>4</inf> receptor stimulation.