Inactivation of Glucagon by Plasma Membranes of Rat Liver
Year: 1972
Type: article
Abstract: Liver plasma membranes rapidly convert glucagon, at physiological concentrations, to a substance that no longer binds to its specific binding sites or activates adenylate cyclase. Inactivation occurs in the presence of albumin and is not completely blocked by a 1000-fold excess of insulin, adrenocorticotropic hormone, and secretin. Des-His-glucagon, which competitively inhibits binding of glucagon and activation of adenylate cyclase by the hormone, binds to liver membranes with an affinity approximately one-tenth that of glucagon. Binding of des-His-glucagon is also reduced after incubation with liver membranes but to a much lesser extent than is the binding of glucagon. As previously found for the processes of glucagon binding and activation of adenylate cyclase, the process of inactivation of glucagon is blocked by treatment of liver membranes with heat, urea, trypsin, or phospholipase A. The specific activity of the glucagon-inactivation process increases to the same extent as does glucagon-stimulated adenylate cyclase activity in the membranes compared to a 1500 x g sediment of liver homogenate. Dipeptidyl aminopeptidase I, a soluble liver enzyme which can degrade glucagon, is present in the membrane fraction but is not responsible for glucagon inactivation by the membranes, to which the inactivation process is firmly bound. The product of glucagon inactivation has not been identified but is very similar to glucagon in its chromatographic behavior and appears not to be des-His-glucagon. These findings indicate that liver plasma membranes may be an important site for specific inactivation of glucagon. A possible relationship between the glucagon inactivation process and the receptor for glucagon is discussed.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1505117697