Interactions of Glucagon, Gut Glucagon, Vasoactive Intestinal Polypeptide and Secretin with Liver and Fat Cell Plasma Membranes: Binding to Specific Sites and Stimulation of Adenylate Cyclase1

To investigate the interactions of pancreatic glucagon, gut glucagon, Vasoactive Intestinal Polypeptide (VIP) and secretin with liver and fat, the binding of the peptides to specific sites and the stimulation of adenylate cyclase were studied in the plasma membrane fraction. Binding studies indicated that the receptor sites for pancreatic glucagon are clearly distinct from the sites for VIP and secretin in both tissues: unlabeled VIP and secretin did not affect the 125I-glucagon binding, and unlabeled glucagon was without effect on the 125I-VIP and I25I-secretin binding. In contrast, secretin and VIP appear to share a common binding site in both tissues: unlabeled secretins (natural and synthetic) were capable of displacing the (m)I-VIP and unlabeled VIP inhibited the binding of 125I-secretin. Gut glucagon inhibited the binding of 125I-glucagon as well as that of 125I-VIP and 125I-secretin in both tissues. In the 125I-glucagonbinding systems, the inhibitory effect of gut glucagon, which contrasts sharply with the lack of effect of VIP and secretin, indicates that pancreatic and gut glucagons share a ommon binding site. In liver membranes, pancreatic glucagon was the most effective in stimulating adenylate cyclase; gut glucagon produced about 70% and VIP 15-20% of the maximum stimulation elicited by pancreatic glucagon. In fat cell membranes, VIP was more potent than pancreatic glucagon and secretin. Th e presence of VIP or of a VIP-like component in the gut glucagon can partly explain the high degree of potency of gut glucagon i n stimulating adenylate cyclase in fat cell membranes. (Endocrinology95: 713, 1974)