Deficiency of cardiac beta-adrenergic receptor in streptozocin-induced diabetic rats.
The number of beta-adrenergic receptors in cardiac myocytes isolated from rats made diabetic with streptozocin (STZ) for 10 wk was measured by use of a hydrophilic nonselective antagonist [3H]CGP 12177 and was found to decrease to 59% of the number in control rats (P less than .05), without any change in affinity. Similarly, using [125I]iodocyanopindolol as a ligand, we found a decrease in the beta-adrenergic-receptor number on cardiac plasma membrane isolated from the diabetic rats [29% decrease (P less than .05) at 1 wk, 50% (P less than .01) at 3 wk, and 49% (P less than .01) at 10 wk compared with control rats]. However, the serum triiodothyronine level that had been known to modulate the beta-adrenergic-receptor-adenylate cyclase system was decreased in the 1-wk-diabetic rats but not in the 10-wk-diabetic rats compared with each control group. Furthermore, there was no difference in urinary catecholamine excretion between diabetic and control groups. In the 10-wk-diabetic rats, the response of adenylate cyclase to isoproterenol was significantly defective (56% decrease compared with control rats; P less than .05), although both the basal and the forskolin-stimulated maximum adenylate cyclase activities and a half-maximum concentration of isoproterenol for the stimulation of adenylate cyclase were similar in control and diabetic rats. On the other hand, both cholera toxin-dependent and islet-activating protein-dependent [32P]NAD incorporations into cardiac plasma membrane were markedly increased in the diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Nishio
Y
Y
Third Department of Medcine, Shiga University of Medical Science, Japan.
Kashiwagi
A
A
Kida
Y
Y
Kodama
M
M
Abe
N
N
Saeki
Y
Y
Shigeta
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values
D008565:Membrane Proteins; D011943:Receptors, Adrenergic, beta; D009243:NAD; D002772:Cholera Toxin; D000262:Adenylyl Cyclases