Is the CCK-8 induced relaxation of the feline sphincter of Oddi mediated by VIP neurons?

The regional, intraarterial, injection of CCK-8 elicits reciprocal effects on the motility of the extrahepatic biliary tree in the cat: the contraction of the gallbladder and a relaxation of the sphincter of Oddi as well as of the duodenal wall. After neural blockade with tetrodotoxin the responses of the sphincter to CCK-8 were blocked, and the responses of the gallbladder were markedly reduced. After the regional administration of a VIP antiserum the sphincter relaxation in response to CCK-8 was blocked. Immunocytochemically it was demonstrated that the feline sphincter contains a rich VIP-ergic innervation, while CCK-like immunoreactivity was found only in mucosal endocrine cells. The results indicate that CCK-8 selectively activates inhibitory VIP neurons innervating the sphincter. After the administration of a nonpeptide CCK-receptor antagonist, the CCK-8 induced motor responses of both the sphincter and the gallbladder were markedly reduced. This indicates that blockade of CCK-8 receptors involves muscular as well as neural CCK-receptors.