DIABETES-INDUCED CHANGES IN THE GI-MODULATED MUSCARINIC RECEPTOR-ADENYLYL CYCLASE SYSTEM IN RAT MYOCARDIUM

The inhibitory guanine nucleotide binding regulatory protein (Gi)-medi ated muscarinic receptor-adenylyl cyclase system was studied in myocar dium from adult male Wistar rats with 10 weeks of diabetes induced by a single intravenous injection of streptozotocin (60 mg/kg). Neither t he messenger ribonucleic acid level nor the amount of Gi was changed i n the streptozotocin diabetic group as compared to the control group. The activity of the adenylyl cyclase stimulated by guanyliminodiphosph ate was decreased by 48% in the streptozotocin diabetic group whereas stimulated activities of adenylyl cyclase by sodium fluoride and forsk olin remained unchanged. The inhibition of forskolin-stimulated adenyl yl cyclase activity by carbachol was more potent in membranes from the streptozotocin diabetic group than that in membranes from the control group. The competition binding curve between (H-3)-quinuclidinyl benz ilate and carbachol obtained from the streptozotocin diabetic group wa s shifted to the left as compared Co the control group. These results suggest that the myocardium of streptozotocin-induced diabetic rats ex hibited an increase in Gi function as demonstrated by the increased in hibition of guanyliminodiphosphate-mediated adenylyl cyclase and the s uperhigh affinity for carbachol of the muscarinic receptors. As there were signs, similar to those seen in clinical heart failure, in the st reptozotocin diabetic group, these results demonstrate that functional alteration of Gi might underlie, at least in part, the cardiac dysfun ction that is associated with diabetes.