Hormone sensitivity of adenylate cyclase activity in cardiac sarcolemma and sarcoplasmic reticulum preparations

Abstract

The functional significance of the adenylate cyclase activity found in cardiac microsomal preparations enriched in sarcoplasmic reticulum vesicles was examined by comparing the effects of agents known to modify this enzyme in sarcolemmal and sarcoplasmic reticulum fractions prepared from guinea pig ventricles. The sensitivity of the sarcolemmal adenylate cyclase to adrenergic agonists resembled that of a typical β-receptor. Although the response to these agonists was similar in the case of the sarcoplasmic reticulum enzyme, the extent of stimulation was much less than in the sarcolemma. The pH optimum of the sarcoplasmic reticulum enzyme of 7.5 was slightly lower than that of the sarcolemmal enzyme, which was 8.0; and NaF shifted the pH optimum of the latter, but not the former. The sarcoplasmic reticulum adenylate cyclase was less sentitive to alkali metal salts and GTP than was the sarcolemmal enzyme. While these studies cannot exclude the possibility that the lesser response of the sarcoplasmic reticulum enzyme to catecholamines, alkali metal salts, and GTP arose from contaminating sarcolemmal fragments that were modified during the preparation of these subcellular fractions, they are consistent with the view that the cardiac cell sarcoplasmic reticulum contains an adenylate cyclase that is less regulated, or regulated by different factors, than those which modulate sarcolemmal adenylate cyclase.