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β-肾上腺素能受体在白色、红色和中间型骨骼肌的肌纤维类型及阻力小动脉中的分布。

Beta-adrenergic receptor distribution among muscle fiber types and resistance arterioles of white, red, and intermediate skeletal muscle.

作者信息

Martin W H, Murphree S S, Saffitz J E

机构信息

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.

出版信息

Circ Res. 1989 Jun;64(6):1096-105. doi: 10.1161/01.res.64.6.1096.

Abstract

The pathophysiological effects of congestive heart failure and physiological effects of exercise training on skeletal muscle may be mediated in part by modulation of beta-adrenergic receptor density. To shed light on the physiological role of skeletal muscle beta-receptors, their density and distribution were characterized in muscle fibers and resistance arterioles of whole tissue slices of three rat hindquarter muscles differing markedly in fiber type composition and capacities for oxidative metabolism and vasodilatation. Binding isotherms and quantitative light microscopic autoradiographic localization of receptors were performed by incubating tissue slices in selected concentrations of [125I]cyanopindolol with and without 10(-5) M l-propranolol. Muscle fiber types were delineated in adjacent sections by histochemical staining of myofibrillar ATPase activity at pH 4.5-4.55. The total tissue content of receptors (Bmax) was nearly threefold greater in the soleus, a muscle consisting almost entirely of slow-twitch (type I) fibers than in superficial white vastus lateralis, a muscle composed of greater than 95% fast-twitch (type IIb) fibers. Bmax was intermediate in gastrocnemius, a mixed fiber muscle (all differences p less than 0.01). Receptor affinity for radioligand was higher in the white vastus than in the mixed fiber and slow-twitch muscles (Kd = 3.5 +/- 0.4 pM for white vastus versus 6.8 +/- 0.8 and 6.4 +/- 1.1 pM in gastrocnemius and soleus, respectively; both p less than 0.01 versus white vastus). Disparities in Bmax among muscles were due entirely to differences in receptor densities of skeletal muscle cells as shown autoradiographically. Furthermore, variations in Bmax of the three skeletal muscles were directly related to percentage of type I fibers (r = 0.99; p less than 0.001), which had a beta-receptor density that was approximately 4.5-fold greater than in superficially located type IIb fibers, 3.2-fold greater than in intermediate depth type IIb fibers, and 2.0-fold greater than in type IIa fibers. In contrast, grain densities of resistance arterioles were similar regardless of surrounding skeletal muscle fiber type composition. However, resistance arterioles were 2.5- and 6.1-fold more numerous in the slow-twitch soleus than in the gastrocnemius and superficial white vastus, respectively (all differences p less than 0.01). We conclude that beta-receptor density of rat hindquarter skeletal muscles is directly proportional to percentage of slow-twitch fibers, while receptor affinity for antagonist is higher in fast-twitch than in slow-twitch or mixed fiber muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

充血性心力衰竭的病理生理效应以及运动训练对骨骼肌的生理效应可能部分是由β-肾上腺素能受体密度的调节介导的。为了阐明骨骼肌β受体的生理作用,对三种大鼠后肢肌肉全组织切片的肌纤维和阻力小动脉中的β受体密度及分布进行了表征,这三种肌肉在纤维类型组成、氧化代谢能力和血管舒张能力方面有显著差异。通过将组织切片在含有和不含有10(-5)M l-普萘洛尔的选定浓度的[125I]氰吲哚洛尔中孵育,进行受体的结合等温线和定量光学显微镜放射自显影定位。通过在pH 4.5 - 4.55下对肌原纤维ATP酶活性进行组织化学染色,在相邻切片中描绘肌纤维类型。比目鱼肌(一种几乎完全由慢肌纤维(I型)组成的肌肉)的受体总组织含量(Bmax)几乎是外侧浅白股四头肌(一种由超过95%的快肌纤维(IIb型)组成的肌肉)的三倍。Bmax在腓肠肌(一种混合纤维肌肉)中处于中间水平(所有差异p均小于0.01)。白色股四头肌中受体对放射性配体的亲和力高于混合纤维和慢肌纤维肌肉(白色股四头肌的Kd = 3.5 +/- 0.4 pM,而腓肠肌和比目鱼肌分别为6.8 +/- 0.8和6.4 +/- 1.1 pM;与白色股四头肌相比,两者p均小于0.01)。如放射自显影所示,肌肉间Bmax的差异完全是由于骨骼肌细胞受体密度的不同。此外,三种骨骼肌Bmax的变化与I型纤维的百分比直接相关(r = 0.99;p小于0.001),I型纤维的β受体密度比浅表的IIb型纤维大约高4.5倍,比中间深度的IIb型纤维高3.2倍,比IIa型纤维高2.0倍。相比之下,无论周围骨骼肌纤维类型组成如何,阻力小动脉的颗粒密度相似。然而,慢肌比目鱼肌中的阻力小动脉数量分别比腓肠肌和外侧浅白股四头肌多2.5倍和6.1倍(所有差异p均小于0.01)。我们得出结论,大鼠后肢骨骼肌的β受体密度与慢肌纤维的百分比成正比,而快肌纤维肌肉中受体对拮抗剂的亲和力高于慢肌纤维或混合纤维肌肉。(摘要截短于250字)

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