RECEPTORS FOR CHOLECYSTOKININ AND GASTRIN PEPTIDES DISPLAY SPECIFIC BINDING-PROPERTIES AND ARE STRUCTURALLY DIFFERENT IN GUINEA-PIG AND DOG PANCREAS

In the light of the strong potency of gastrin‐related peptides on pancreatic exocrine secretion in dog, we analyzed the binding properties of peptides related to cholecystokinin (CCK) and gastrin on dog pancreatic acini compared to guinea‐pig acini. Moreover, we determined apparent molecular masses of photoaffinity labelled CCK/gastrin receptors in the two models. Using the CCK radioligand, receptor selectivity towards CCK/gastrin agonists and antagonists was found to be lower in dog acini than in guinea‐pig acini. Performing the binding with CCK and gastrin radioligands in combination with N2,O2′‐dibutyryl‐guanosine 3′,5′‐monophosphate, revealed that in dog acini there exist two different sub‐classes of CCK/gastrin receptors having high and low selectivity, the latter ones being able to bind gastrin with high affinity (Kd= 2.1 nM). SDS‐PAGE analysis of covalently cross‐linked receptors using several photosensitive CCK and gastrin probes of different peptide chain lengths demonstrated that in guinea‐pig, CCK peptides bound to a 84‐kDa component whereas in dog pancreas, CCK and gastrin peptides bound to three distinct molecular species (Mr∼ 78000, 45000, 28000). Performing crosslinking in the presence of 1 μM CCK indicated that a 45‐kDa protein is the putative CCK/gastrin receptor in dog pancreas. Our results support the concept of heterogeneity of CCK/gastrin receptors. Copyright © 1987, Wiley Blackwell. All rights reserved