Effect of cholecystokinin and the octapeptide of cholecystokinin on the feline sphincter of Oddi and gallbladder. Mechanisms of action.

A C T WVe studied the effect of cholecysto- kinin (CCK) and the octapeptide of cholecystokinin (OP-CCK) on the feline gallbladder and sphincter of Oddi.Both CCK caused a dose-dependent gallbladder contraction and sphincter of Oddi relaxation.The half- maximal responses of the sphincter of Oddi were 6 ng/kg for OP-CCK and 0.15 Ivy-dog U/kg for CCK, which were lower than those ofthe gallbladder wvith 28 ng/kg and 0.32 Ivy-dog U/kg, respectively.The effect of OP-CCK on the gallbladder was partially blocked by tetrodotoxin (P < 0.02), hexamethonium alone (P < 0.05), or a combination of hexamethonium and atropine (P < 0.01).The gallbladder response to CCK wvas not blocked by either atropine alone (P < 0.60) or adrenergic anitagonists (P > 0.40).The sphincter of Oddi response to OP-CCK was blocked by tetrodotoxin (P < 0.001) but it was not blocked by cholinergic (P < 0.20) or adrenergic antagonists (P < 0.60).After comiplete denervation with tetrodotoxin, OP-CCK caused sphincter of Oddi contraction.These findings indicate that there are two excitatory receptors for CCK in the gallbladder, one at the cholinergic neurons and the other at the level of the gallbladder muscle.There are also tvvo receptors for CCK in the sphincter of Oddi, one that is inhibitory, and present at the noncholinergic, nonadrenergic neurons, and the other, excitatory, at the circular muscle.