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Abstract

Altered muscarinic receptor properties and function in the heart in diabetes.

G O Carrier and R S Aronstam
Journal of Pharmacology and Experimental Therapeutics August 1987, 242 (2) 531-535;
G O Carrier
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R S Aronstam
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Abstract

The cardiac cholinergic system was studied in streptozotocin (STZ)-diabetic and age-matched control rats. STZ-diabetic rats (8-10 weeks) were supersensitive to the negative chronotropic effects of acetylcholine, carbamylcholine and bethanechol; inotropic responses to these muscarinic agonists were unaltered. This phenomenon was associated with a decrease in acetylcholinesterase activity but no change in the rate and extent of neuronal choline uptake. [3H]N-methylscopolamine bound to muscarinic receptors in atria from both groups of rats with the same high affinity. The density of [3H]N-methylscopolamine binding sites, however, was 34% lower in atria from STZ-diabetic rats. Agonist binding affinity was lower in diabetes; carbamylcholine had a lower affinity for both the high- and low-affinity receptors. These results indicate that cardiac cholinergic supersensitivity in right atria in diabetes occurs before the development of autonomic neuropathy insofar as neuronal [3H]choline uptake is unaltered at this stage of STZ diabetes. Changes in agonist binding conformation, without a concomitant change in antagonist binding affinity, suggest that supersensitivity of right atria to muscarinic agonist may be a consequence of altered coupling of muscarinic receptor to transduction mechanisms involved in chronotropism in diabetes.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 242, Issue 2
1 Aug 1987
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Abstract

Altered muscarinic receptor properties and function in the heart in diabetes.

G O Carrier and R S Aronstam
Journal of Pharmacology and Experimental Therapeutics August 1, 1987, 242 (2) 531-535;

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Abstract

Altered muscarinic receptor properties and function in the heart in diabetes.

G O Carrier and R S Aronstam
Journal of Pharmacology and Experimental Therapeutics August 1, 1987, 242 (2) 531-535;
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