Supersensitivity of isolated atria from diabetic rats to adenosine and methacholine: modulation by pertussis toxin.
The chronotropic response of isolated right atria obtained from rats made diabetic 14-15 weeks previously by streptozotocin, was compared with age-matched controls. Diabetic rat atria are significantly more sensitive to the negative chronotropic actions of adenosine and of methacholine. Pretreating both control and diabetic rats with 2.5 mg kg-1 pertussis toxin attenuated the negative chronotropic effects of methacholine and adenosine on isolated atria, although diabetic atria still displayed a significantly greater sensitivity to these agonists (P less than 0.05-0.001). The negative chronotropic effects of methacholine and adenosine on both control and diabetic atria were abolished following pretreatment with higher doses of pertussis toxin (10 mg kg-1). These results suggest that pertussis toxin-sensitive G proteins may be involved in the supersensitivity of diabetic hearts to methacholine and adenosine.
Li
X J
XJ
Department of Pharmacology, Oregon Health Sciences University, Portland 97201-3098.
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D001786:Blood Glucose; D010566:Virulence Factors, Bordetella; D016210:Methacholine Chloride; D013311:Streptozocin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine