摘要：

Glucagon and fluoride ion stimulate the activity of a com- mon adenyl cyclase system in plasma membranes isolated from rat liver. Their actions are noncompetitive indicating that they act at separate sites in this system. Manganous ion, above 5.0 mu, inhibited selectively the response of the enzyme to glucagon. Inorganic pyrophosphate (1.5 nnu), on the other hand, inhibited the response of the enzyme to fluoride but enhanced the response to glucagon. The in- hibitory effect of pyrophosphate was noncompetitive with fluoride ion. Highly purified phospholipase A caused a selec- tive loss of the glucagon response and enhanced the stimula- tory effect of fluoride ion. Treatment of liver membranes with digitonm also caused a selective loss of hormone re- sponse. Inactivation of glucagon response by digitonin was not restricted to the liver membrane adenyl cyclase system; incubation of ghosts of fat cells with digitonin resulted in loss of response of the adenyl cyclase system to glucagon, adreno- corticotropin, secretin, and epinephrine at very low concen- trations of the detergent. Digitonin enhanced the response of the fat cell system to fluoride ion. Sodium dodecyl sulf- ate, over a narrow range of concentrations, inhibited the re- sponse of liver membrane adenyl cyclase to glucagon, and enhanced the enzyme's response to fluoride ion. Other detergents caused a parallel loss of the response to both fluoride ion and glucagon.The present findings suggest that glucagon and fluoride ion activate adenyl cyclase by different mechanisms. It is pos- sible that these agents react through different molecular entities in this complex enzyme system.

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