Wu L L, Tang C, Liu M S
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Missouri 63104, USA.
Shock. 1997 May;7(5):318-23. doi: 10.1097/00024382-199705000-00002.
Alterations in the distribution of alpha-adrenergic receptors (alpha ARs) in two subcellular organelles, the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). alpha ARs were assayed by using [3H]prazosin binding and photoaffinity labeling with [125I]arylazidoprazosin in combination with polyacrylamide gel electrophoresis. Septic rat hearts exhibit two distinct phases: an initial hypercardiodynamic (9 h after CLP; early sepsis) followed by a hypocardiodynamic (18 h after CLP; late sepsis) phase. [3H]prazosin binding studies show that during early sepsis, the Bmax (maximal binding capacity) was increased by 21.4% in sarcolemma but was decreased by 22.5% in light vesicles, while during late sepsis, the Bmax was decreased by 25.4% in sarcolemma but was increased by 60.8% in light vesicles. The photoaffinity labeling studies revealed three binding peptides with M(r) of 77, 68, and 39 kDa. The total binding for the three label peptides during early sepsis was increased by 25.5% in sarcolemma but was decreased by 40% in light vesicles, while during late sepsis, the total binding was decreased by 32.1% in sarcolemma but was increased by 35.8% in light vesicles. These data indicate that alpha ARs in the rat heart were externalized from light vesicles to sarcolemma during early hypercardiodynamic phase while they were internalized from surface membranes to intracellular compartment during late hypocardiodynamic phase of sepsis. Because alpha ARs play an important role in regulating myocardial contractility, an initial externalization followed by internalization of alpha ARs may contribute to the development of the initial hypercardiodynamic and the subsequent hypocardiodynamic states during sepsis.
研究了脓毒症进展过程中大鼠心脏两个亚细胞器（肌膜和轻囊泡）中α-肾上腺素能受体（αARs）分布的变化。通过盲肠结扎和穿刺（CLP）诱导脓毒症。使用[3H]哌唑嗪结合以及[125I]芳基叠氮哌唑嗪的光亲和标记结合聚丙烯酰胺凝胶电泳来测定αARs。脓毒症大鼠心脏表现出两个不同阶段：最初的高心动力阶段（CLP后9小时；早期脓毒症），随后是低心动力阶段（CLP后18小时；晚期脓毒症）。[3H]哌唑嗪结合研究表明，在早期脓毒症期间，肌膜中的Bmax（最大结合能力）增加了21.4%，而轻囊泡中的Bmax降低了22.5%；而在晚期脓毒症期间，肌膜中的Bmax降低了25.4%，而轻囊泡中的Bmax增加了60.8%。光亲和标记研究揭示了三种分子量分别为77、68和39 kDa的结合肽。在早期脓毒症期间，肌膜中三种标记肽的总结合增加了25.5%，而轻囊泡中减少了40%；而在晚期脓毒症期间，肌膜中的总结合减少了32.1%，而轻囊泡中增加了35.8%。这些数据表明，在脓毒症早期高心动力阶段，大鼠心脏中的αARs从轻囊泡外化至肌膜，而在晚期低心动力阶段，它们从表面膜内化至细胞内区室。由于αARs在调节心肌收缩力中起重要作用，αARs最初的外化随后的内化可能有助于脓毒症期间最初的高心动力状态和随后的低心动力状态的发展。
