Effects of Acute Ketotic and Non-ketotic Diabetes on the Myocardial Muscarinic Receptors

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Abstract
Myocardial membranes from rats rendered diabetic with streptozotocin were used to determine muscarinic receptors with 3H-quinuclidinyl benzilate. In the acute state of diabetes, 4 days after induction, the density of receptors were equal in controls, insulin (glucosuria) and non-insulin-treated (glucosuria and ketonuria) diabetic animals. In myocardial membranes from diabetic rats agonist binding to the muscarinic receptor was shifted to higher affinity than in controls. Computer modeling revealed that guanine nucleotides transformed agonist binding from 2 sites to a site of low affinity in controls. In membranes from insulin-treated diabetic animals, the shift to lower affinity occurred but 2 receptor sites remained. In non-insulin-treated membranes, the nucleotides failed to exert any effect. Inhibition of adenylate cyclase by the muscarinic agonist oxotremorine was amplified in diabetic membranes. The function of the inhibitory nucleotide binding protein (N1), as reflected by agonist binding to the receptor and adenylate cyclase inhibition, was sensitive to the hormonal status.

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