Mechanisms of adaptive supersensitivity: correlation of guinea pig atrial supersensitivity with modifications in adenylyl cyclase activity.
The possibility that the cellular mechanism underlying adaptive supersensitivity in right and left atria of the guinea pig may involve either adenylyl cyclase or components of that transduction process was examined in left and right atria obtained from controls or guinea pigs chronically treated with reserpine. Adenylyl cyclase activity and the abundance of alpha-subunits of several G-proteins (i.e. Gs, Gi, and Go) were quantified using standard techniques. Functional concentrations of Gs and Gi were compared in tissues from control and treated animals using pertussis- or cholera toxin-induced protein ribosylation. Chronic treatment with reserpine did not alter basal levels of adenylyl cyclase activity in left or right atrium but did increase significantly the ability of isoproterenol, 5'-guanylylimido diphosphate, and forskolin to activate adenylyl cyclase in the left atrium compared with the control. In contrast, treatment with reserpine increased the ability of only isoproterenol to active adenylyl cyclase in the right atrium. The increases in enzyme activation were not correlated with any detectable change in the concentrations of G-proteins or beta-adrenoceptors. The correlation between the specificity of changes in responsiveness and increased activation of adenylyl cyclase suggests that the cellular mechanism that underlies the development of adaptive supersensitivity in the guinea pig myocardium may involve a modification of adenylyl cyclase. The data also support the idea that the development of enhanced responsiveness in cardiac muscle may not only involve more than one cellular mechanism but may even differ between right and left atrium and ventricles of the same species.
Roberts
M I
MI
Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown 26506-9223, USA.
Stadel
J M
JM
Torphy
T J
TJ
Fleming
W W
WW
Taylor
D A
DA
D000222:Adaptation, Physiological; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019204:GTP-Binding Proteins / Q000032:analysis; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D000246:Adenosine Diphosphate Ribose; D012110:Reserpine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases