The regulation of adenylate cyclase in adipocyte plasma membrane from genetically obese (ob/ob) mice.

Adenylate cyclase activity was determined using a purified plasma membrane fraction prepared from isolated adipocytes by a Percoll gradient centrifugation procedure. The activation of adenylate cyclase by isoprenaline was reduced by approximately 50% in membranes from obese mice, although no reduction in the sensitivity of the response was apparent. Basal and fluoride- and 5'-guanylyl-imidodiphosphate-stimulated activities were similar in both groups. However, two defects in the obese system were identified which suggested that an alteration in the properties of the regulatory protein may account for the impaired hormonal activation. The specific binding of 3H-dihydroalprenolol to membranes from obese animals also was decreased, suggesting a reduction in the number of beta-adrenergic receptors.