Externalization and internalization of cardiac endothelin receptors during different phases of sepsis in rat.

OBJECTIVE: To study the redistribution of endothelin-1 (ET-1) receptors in two subcellular organelles, the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP). ET1 receptor was assayed by using [125I]-ET1 binding. Marker enzyme activities, protein yield, and dry-to-wet weight ratio of cardiac membranes were measured. RESULTS: Septic rat heart exhibited two distinct phases: an initial hyperdynamic phase( 9h after CLP; early stage of sepsis) followed by a hypodynamic (18h after CLP, late stage of sepsis) phase. [125I]-ET1 binding study showed that during early stage of sepsis, the B(max) of ET1 receptors was increased by 30% in sarcolemma but decreased by 19% in light vesicles, while during late stage of sepsis, the B(max) was decreased by 24% in sarcolemma but increased by 38% in light vesicles. The total binding of sarcolemma and light vesicles was increased by 25% during early stage of sepsis but decreased by 17% during late stage of sepsis. CONCLUSIONS: These data indicated that ET1 receptors in the rat heart were externalized from light vesicles to sarcolemmal membranes during early hyperdynamic phase while internalized from surface membranes to intracellular compartment during late hypodynamic phase of sepsis.