Alloxan-induced diabetes reduces beta-adrenergic receptor number without affecting adenylate cyclase in rat ventricular membranes.
We have investigated alterations in beta-adrenergic receptors and adenylate cyclase activity in myocardial membranes from normal and alloxan-treated diabetic rats. Saturation curves of [3H]dihydroalprenolol binding yielded a Bmax of 96.3 +/- 3.9 fmol/mg protein in normal membranes and 47.6 +/- 3.9 fmol/mg protein in diabetic membranes. Decreased receptor number in membranes from diabetic animals was not accompanied by alteration in receptor affinity for either antagonists or agonists to the beta-receptor. We were unable to detect any alteration in adenylate cyclase activity in similar ventricular membranes. Adenylate cyclase activity in the basal state or in the presence of sodium fluoride, guanyl-5'-yl imidodiphosphate, or isoproterenol, with or without GTP, was not altered by the alloxan-induced diabetic state. Stimulation of adenylate cyclase activity by forskolin, the novel diterpene activator, also was not altered by diabetes. The results suggest that while diabetes reduced beta-receptor number, this is not reflected in any other component of the adenylate cyclase complex.
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D002118:Calcium / Q000032:analysis; D005576:Colforsin; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000032:analysis*; D011943:Receptors, Adrenergic, beta / Q000032:analysis*
D004224:Diterpenes; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D004082:Dihydroalprenolol; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D002118:Calcium