MECHANISMS OF ADAPTIVE SUPERSENSITIVITY - CORRELATION OF GUINEA-PIG ATRIAL SUPERSENSITIVITY WITH MODIFICATIONS IN ADENYLYL-CYCLASE ACTIVITY

The possibility that the cellular mechanism underlying adaptive supers ensitivity in right and left atria of the guinea pig may involve eithe r adenylyl cyclase or components of that transduction process was exam ined in left and right atria obtained from controls or guinea pigs chr onically treated with reserpine. Adenylyl cyclase activity and the abu ndance of alpha-subunits of several G-proteins (i.e. G(s), G(i), and G (o)) were quantified using standard techniques. Functional concentrati ons of G(s) and G(i) were compared in tissues from control and treated animals using pertussis- or cholera toxin-induced protein ribosylatio n. Chronic treatment with reserpine did not alter basal levels of aden ylyl cyclase activity in left or right atrium bur did increase signifi cantly the ability of isoproterenol, 5'-guanylylimido diphosphate, and forskolin to activate adenylyl cyclase in the left atrium compared wt ih the control. rn contrast, treatment with reserpine increased the ab ility of only isoproterenol to active adenylyl cyclase in the right at rium. The increases in enzyme activation were not correlated with any detectable change in the concentrations of G proteins or beta-adrenoce ptors. The correlation between the specificity of changes in responsiv eness and increased activation of adenylyl cyclase suggests that the c ellular mechanism that underlies the development of adaptive supersens itivity in the guinea pig myocardium may involve a modification of ade nylyl cyclase. The data also support the idea that the development of enhanced responsiveness in cardiac muscle may not only involve more th an one cellular mechanism but may even differ between right and left a trium and ventricles of the same species. Copyright (C) 1997 Elsevier Science Inc.