Sr. Silbiger et al., DEFECTIVE GLOMERULAR BETA-ADRENERGIC SIGNAL TRANSMISSION IN SPONTANEOUSLY DIABETIC RATS, The Journal of laboratory and clinical medicine, 124(2), 1994, pp. 249-254
Citations number
33
Categorie Soggetti
Medical Laboratory Technology","Medicine, General & Internal
Previous studies in experimental diabetes have demonstrated cardiovasc
ular abnormalities of the beta-adrenergic system and reduced adrenergi
cally stimulated renal renin secretion. To examine the defect in the b
eta-adrenergic signal, glomerular cyclic adenosine monophosphate (cAMP
) levels were measured in response to isoproterenol and other humoral
agonists (coincubated with the phosphodiesterase inhibitor isomethylxa
nthine) in nondiabetic and diabetic BB/Wor rats. Basal (unstimulated)
levels of glomerular cAMP did not differ between control and diabetic
BB/Wor rats, nor did cAMP accumulation differ on incubation with the h
umoral agonists PGE(2) and histamine. However, on incubation with vari
ed concentrations of the nonselective beta-adrenergic agonist isoprote
renol, control glomeruli demonstrated a twofold increase in cAMP while
a negligible response was observed in diabetic glomeruli. Peak levels
of cAMP were higher in control (192 +/- 24 pmol/mg protein) than in d
iabetic (141 +/- 8 pmol/mg protein) glomeruli Ip < 0.01). No differenc
es were observed on incubation with the adenylate cyclase stimulator f
orskolin. Measurement of glomerular beta-adrenoreceptors by coincubati
on with iodine 125-labeled cyanopindolol demonstrated no differences i
n either receptor number (B-max) or affinity (K-D). These data indicat
e that a specific defect in beta-adrenergic signalling exists in glome
rular tissue from spontaneously diabetic rats. Because no decrease in
forskolin-stimulated adenylate cyclase was observed, defective couplin
g of the receptor to its effector, perhaps through the guanine nucleot
ide stimulatory protein, may account for these observations.