Affiliation:
1. Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63104, USA.
Abstract
Changes in the distribution of beta-adrenergic receptors in two subcellular fractions, the sarcolemma and the light vesicle, of rat heart during sepsis were studied, using [3H]dihydroalprenolol ([3H]DHA) binding and photoaffinity labeling with [125I]iodocyanopindolol ([125I]ICYP). Sepsis was induced by cecal ligation and puncture (CLP). Septic rat hearts exhibit an initial hypercardiodynamic (9 h after CLP; early sepsis) and a subsequent hypocardiodynamic (18 h after CLP; late sepsis) state. [3H]DHA-binding studies show that, during early sepsis, the maximum binding capacity (Bmax) was increased by 35% in sarcolemma but was decreased by 25% in light vesicles, whereas during late sepsis, the Bmax was decreased by 39% in sarcolemma but was increased by 30% in light vesicles. Photoaffinity labeling studies show that the incorporation of [125I]ICYP into 64,000-Da peptide during early sepsis was increased by 32% in sarcolemma but was decreased by 27% in light vesicles, whereas during late sepsis, the incorporation was decreased by 30% in sarcolemma but was increased by 35% in light vesicles. These data indicate that beta-adrenergic receptors in the rat heart were externalized from light vesicles to sarcolemma during the hyperdynamic phase but were internalized from surface membranes to intracellular sites during the hypodynamic phase of sepsis. Because beta-adrenergic receptors mediate adrenergic control of cardiac muscle contraction, a biphasic intracellular redistribution of beta-adrenergic receptors in the heart may contribute to the development of the initial hypercardiodynamic and subsequent hypocardiodynamic states during sepsis.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
74 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献