Evidence that relaxation of hog biliary muscle is mediated by the interaction between the protein inhibitor of cyclic AMP dependent protein kinase and cholecystokinin C-terminal peptides

Abstract

The interaction of various cholecystokinin (CCK) peptides with the protein inhibitor (PK-I) of cyclic AMP dependent protein kinase (A-PK) has been studied. The order of the affinities ( ed 50) for relaxation of hog biliary muscle by a series of C-terminal peptides of CCK correlated with the order of the potencies for A-PK-catalyzed phosphorylation of the sarcoplasmic reticulum enriched fraction (SR-F) in the muscle. CCK-4 peptide inhibited the PK-I of A-PK. The apparent K m value of the peptide was 11.5 μM. Scatchard plot analysis for the binding of [ 14C]CCK-6 peptide to the PK-I showed a dissociation constant ( K d ) of 11.2 μM. These results indicated that the K d value agreed with the ed 50 value of CCK-6 and the K m value of CCK-4. It is proposed that a receptor for CCK C-terminal peptides is probably a component in the PK-I; binding of the peptides to this site usually results in the relaxation by these allosteric inhibitors of the PK-I.