Effects of malnutrition on rat myocardial beta-adrenergic and muscarinic receptors.

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Abstract
Malnutrition, as well as malignancy, induces alterations in heart metabolism and performance. Previous studies have implicated adrenergic mechanisms as the cause. The present study was undertaken to investigate if the adenylate cyclase system in the rat heart was affected by malnutrition. Three different animal groups with malnutrition were compared with a control group: rats with acute starvation for 14-96 hours, rats with protein-calorie malnutrition for 2 weeks, and rats with tumors. Stimulation by .beta.-adrenergic receptors and inhibition by muscarinic receptors of adenylate cyclase activity were not altered by malnutrition. However, conditions used for in vitro adenylate cyclase determinations were, of necessity, not physiological. Neither did the number of .beta.-adrenergic and muscarinic receptors change. When competition-binding experiments were performed, differences comprising agonist affinity and affinity state distribution were noted among the groups. The myocardial .beta.-adrenergic receptors formed a reduced number of high-affinity sites in all groups as compared with the control rats. All high-affinity sites displayed a more than 10-fold increase in affinity toward isoproterenol and an impaired sensitivity to guanine nucleotides except in heart membranes derived from rats starved less than 48 hours. While the protein-calorie restricted and the tumor-bearing rats had myocardial .beta.-adrenergic receptors that were unresponsive to guanine nucleotides, after 48 hours of starvation the rats exhibited an attenuated guanine-nucleotide-induced affinity shift. No changes associated with malnutrition in myocardial membrane levels of the stimulatory guanine-nucleotide-binding protein were detected by cholera-toxin-induced ADP-ribosylation. In competition binding between quinuclidinyl benzilate and carbachol, myocardial muscarinic receptors derived from malnourished rats exhibited a three-site affinity distribution whereas control rats displayed a two-site affinity distribution. The observations on myocardial .beta.-adrenergic and muscarinic receptors in malnourished rats are consistent with alterations in receptor and regulatory guanine-nucleotide-binding protein interaction. Our results point to the possibility of regulating cell functions by modifying coupling mechanisms. In addition, .beta.-adrenergic receptors displayed a considerably increased affinity towards isoproterenol, which fact may contribute to the earlier findings of .beta.-adrenergic hypersensitivity in malnutrition.