Tang C, Liu M S
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63104, USA.
Am J Physiol. 1996 Jan;270(1 Pt 2):R254-63. doi: 10.1152/ajpregu.1996.270.1.R254.
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.
采用[3H]二氢烯丙洛尔（[3H]DHA）结合法以及用[125I]碘氰吲哚洛尔（[125I]ICYP）进行光亲和标记法，研究了脓毒症大鼠心脏肌膜和轻囊泡这两个亚细胞组分中β-肾上腺素能受体分布的变化。通过盲肠结扎和穿刺（CLP）诱导脓毒症。脓毒症大鼠心脏呈现出初始的高动力状态（CLP后9小时；早期脓毒症）以及随后的低动力状态（CLP后18小时；晚期脓毒症）。[3H]DHA结合研究表明，在早期脓毒症期间，肌膜中的最大结合容量（Bmax）增加了35%，而轻囊泡中的Bmax降低了25%；而在晚期脓毒症期间，肌膜中的Bmax降低了39%，轻囊泡中的Bmax增加了30%。光亲和标记研究表明，在早期脓毒症期间，[125I]ICYP掺入64,000道尔顿肽的量在肌膜中增加了32%，而在轻囊泡中降低了27%；而在晚期脓毒症期间，该掺入量在肌膜中降低了30%，在轻囊泡中增加了35%。这些数据表明，在高动力阶段，大鼠心脏中的β-肾上腺素能受体从轻囊泡转移至肌膜，但在脓毒症的低动力阶段，从表面膜内化至细胞内位点。由于β-肾上腺素能受体介导肾上腺素对心肌收缩的控制，心脏中β-肾上腺素能受体的双相细胞内重新分布可能有助于脓毒症期间初始高动力状态和随后低动力状态的发展。
