Effects of verapamil on the cardiac alpha 1-adrenoceptor signalling system in diabetic rats.
We evaluated the effects of chronic verapamil treatment on the cardiac alpha 1-adrenoceptor signalling system in streptozocin-induced diabetic rats. The decrease in maximum cell surface [3H]bunazosin binding (Bmax) in isolated cardiac myocytes from the diabetic group (-46%, P < 0.01) was completely reversed by a 4-week course of verapamil, while Bmax in the verapamil-treated control group was unchanged. Similarly, the reduction in ventricular inositol 1,4,5-trisphosphate (IP3) production after stimulation with 10 microM noradrenaline (NA) seen in diabetes (-30%, P < 0.01) was completely normalized by verapamil, while the response in the verapamil-treated control group was unaffected. These results indicate that verapamil can induce complete recovery of the impaired cardiac alpha 1-adrenoceptor signalling system in the diabetic heart without affecting glucose metabolism.
Tanaka
Y
Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Kashiwagi
A
A
Saeki
Y
Y
Takagi
Y
Y
Asahina
T
T
Kikkawa
R
R
Shigeta
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007293:Inosine Triphosphate / Q000096:biosynthesis; D007328:Insulin / Q000097:blood; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014700:Verapamil / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D007293:Inosine Triphosphate; D014700:Verapamil; D011493:Protein Kinase C; D009638:Norepinephrine