Mode of action of cholecystokinin octapeptide on smooth muscles of stomach, ileum and gall bladder

Mechanical activity of preparations isolated from canine and guinea-pig stomach, ileum and gall bladder was recorded. At least 2 strips were cut out from each organ and investigated simultaneously in thermostatically controlled organ baths. Responses to acetylcholine (ACH) were used for comparison. Octapeptide of cholecystokinin (CCK-OP) at concentrations of 5 X 10(-11) M to 10(-8) M produced dose-dependent tonic concentrations in all muscle strips and showed a higher affinity but lower efficacy as compared to ACH. Atropine (10(-7) M 10(-5) M) had no effect on the CCK-OP responses in stomach and gall bladder muscle strips but it significantly decreased the CCK-OP responses in ileum muscle strips. Dibutyryl cyclic GMP (dbc GMP) at concentrations of 10(-5) M-5 X 10(-4) M did not change the ACH dose-response curves but shifted to the right in parallel to the control the dose-response curves for CCK-OP in all muscle preparations with pA2 values 5, 5.3, 7.2, and 6 for canine stomach and guinea-pig stomach, ileum and gall bladder, respectively. Michaelis-Menten's analysis suggested a competitive type of interaction of dbc GMP on CCK-OP contractile responses of guinea-pig ileum and gall bladder; at a higher concentration (5 X 10(-4) M) the antagonistic effect of dbc GMP in canine and guinea-pig stomach appeared to be a mixed or uncompetitive type. The data suggest that the contractile effects of CCK-OP in the iliac smooth muscle are caused by cholinergic and direct mechanisms whereas on the gall bladder and gastric smooth muscles by direct myogenic mechanisms only.