Aronstam R S, Carrier G O
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
Diabetes. 1989 Dec;38(12):1611-6. doi: 10.2337/diab.38.12.1611.
Right atria from rats rendered diabetic by injection of streptozocin (STZ-D) for 8-10 wk are supersensitive to the negative chronotropic effects of muscarinic agonists but have decreased levels of muscarinic receptors and acetylcholinesterase activity. Insulin treatment completely prevents the development of these changes. The proportion of atrial muscarinic receptors displaying high-affinity agonist binding is lower in STZ-D rats; however, the sensitivity of high-affinity agonist binding to regulation by a guanine nucleotide (5'-guanylylimidodiphosphate) is greater in atria from diabetic rats. Again, insulin treatment eliminates these differences. These findings indicate that alterations in atrial muscarinic systems in STZ-D rats are a consequence of the elaboration of the diabetic state and suggest that an alteration of functional muscarinic receptor-G protein coupling contributes to the altered physiological responsiveness of the heart in diabetes.
通过注射链脲佐菌素（STZ-D）使大鼠患糖尿病8 - 10周后，其右心房对毒蕈碱激动剂的负性变时作用超敏感，但毒蕈碱受体水平降低且乙酰胆碱酯酶活性下降。胰岛素治疗可完全防止这些变化的发生。在STZ-D大鼠中，显示高亲和力激动剂结合的心房毒蕈碱受体比例较低；然而，糖尿病大鼠心房中高亲和力激动剂结合对鸟嘌呤核苷酸（5'-鸟苷酰亚胺二磷酸）调节的敏感性更高。同样，胰岛素治疗消除了这些差异。这些发现表明，STZ-D大鼠心房毒蕈碱系统的改变是糖尿病状态形成的结果，并提示功能性毒蕈碱受体 - G蛋白偶联的改变导致了糖尿病时心脏生理反应性的改变。
