Initial externalization followed by internalization of [beta] -adrenergic receptors in rat heart during sepsis. Tang, Chaoshu, and Maw-Shung Liu. Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104
APStracts 2:0224R, 1995.
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 labelling with [125I]iodocyanopindolol ([125I]ICYP). Sepsis was induced by cecal ligation and puncture (CLP). Septic rat hearts exhibit an initial hyper-cardiodynamic (9 h after CLP; early sepsis) and a subsequent hypo-cardiodynamic (18 h after CLP; late sepsis) states. [3H]DHA binding studies show that during early sepsis, the Bmax was increased by 35% in sarcolemma but was decreased by 25% in light vesicles; while during late sepsis, the Bmax was decreased by 39% in sarcolemma but was increased by 30% in light vesicles. Photoaffinity labelling 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; while 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 hyperdynamic phase while they were internalized from surface membranes to intracellular sites during 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 hyper- and subsequently the hypo-cardiodynamic states during sepsis. 

Received 26 May 1995; accepted in final form 27 July 1995.
APS Manuscript Number R320-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.