The Glucagon-sensitive Adenyl Cyclase System in Plasma Membranes of Rat Liver

Abstract

Abstract Plasma membranes prepared from rat livers have been treated with digitonin or phospholipase A under conditions which result in substantial loss of glucagon-stimulated adenyl cyclase activity but no loss of fluoride-stimulated activity. These results are thought to reflect extensive modification of the structures responsible for hormone sensitivity without destruction of the catalytic component of the adenyl cyclase system in these membranes. Corresponding decreases in binding of 125I-glucagon to the membranes are observed following digitonin or phospholipase A treatment. Both glucagon sensitivity of adenyl cyclase and binding of 125I-glucagon can be partially restored by exposing treated membranes to aqueous suspensions of membrane lipids. The mechanism of the effects of these lipids has not been established. Pure phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine are all capable of partially restoring glucagon-stimulated adenyl cyclase activity and binding of 125I-glucagon to phospholipase A-treated membranes. Of these, phosphatidylserine produces the greatest effects. Chromatographic fractions of membrane lipids produce positive and negative effects on control and treated membranes which are difficult to interpret. However, it appears that there is some specificity in the effects of the lipid fractions. These results may have significant implications regarding the relationship of adenyl cyclase systems to membrane structure and attempts to purify the components of these systems.