Prolonged activation of alpha 1 adrenoceptors induces down-regulation of protein kinase C in vascular smooth muscle.
Prolonged activation of alpha 1 adrenoceptors induces down-regulation of protein kinase C in vascular smooth muscle.
复制标题
α1 肾上腺素受体的长期激活会导致血管平滑肌中蛋白激酶 C 的下调。
DOI：
10.1097/00005344-199212000-00020
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发表时间：
1992
影响因子：
3
通讯作者：
Hoffman,BB
中科院分区：
文献类型：
--
作者：
Hu,Z;Azhar,S;Hoffman,BB
血管平滑肌持续暴露于儿茶酚胺导致[α] 1-肾上腺素受体介导的血管平滑肌收缩脱敏。本研究旨在确定血管长期暴露于儿茶酚胺对蛋白激酶C（PKC）活性的影响。用10 [mu] M去甲肾上腺素（NE）孵育大鼠主动脉平滑肌4小时，导致大鼠主动脉平滑肌对佛波醇酯4 [beta]-佛波醇12，13-二丁酸酯（PDBu）的收缩反应敏感性降低3倍;这种敏感性的丧失依赖于内皮的存在。NE诱导可溶性和颗粒形式的PKC的酶活性降低45%。使用[3 H] PDBu标记主动脉中的佛波酯受体结合位点，NE处理的血管中的[3 H] PDBu结合位点减少了34%，而对配体的结合亲和力没有变化。为了确定这种酶活性和[3 H] PDBu结合的损失是否是由于酶量的减少，使用针对PKC的单克隆抗体（MoAb）进行Western印迹分析。这种方法证实了大鼠主动脉平滑肌的可溶性组分中存在80-Kd免疫反应性PKC，并证明了持续暴露于儿茶酚胺后血管中PKC的量减少44%。我们的研究结果表明，[α]-肾上腺素能受体在血管中的长期激活，导致PKC的下调，这可能有助于由血管收缩剂介导的收缩脱敏。
Sustained exposure of vascular smooth muscle to catecholamines results in desensitization of [alpha] 1-adrenoreceptor-mediated vascular smooth muscle contraction. The present study was designed to determine the effects of prolonged exposure of blood vessels to catecholamines on protein kinase C (PKC) activity. Incubation of rat aortic smooth muscle with 10 [mu] M norepinephrine (NE) for 4 h resulted in a threefold decrease in sensitivity of the contractile response of rat aortic smooth muscle to the phorbol ester 4 [beta]-phorbol 12, 13-dibutyrate (PDBu); this loss in sensitivity was dependent on the presence of endothelium. NE induced a 45% decrease in enzymatic activity of the soluble and particulate forms of PKC. With [3H] PDBu used to label phorbol ester receptor binding sites in the aorta, there was a 34% decrease in [3H] PDBu binding sites in NE-treated blood vessels without change in binding affinity for the ligand. To determine whether this loss in enzymatic activity and [3H] PDBu binding resulted from a decrease in the quantity of the enzyme, Western blot analyses were performed using a monoclonal antibody (MoAb) against PKC. This approach confirmed the presence of an 80-Kd immunoreactive PKC in the soluble fraction of rat aortic smooth muscle and demonstrated a 44% decrease in the amount of PKC in blood vessels after sustained exposure to catecholamines. Our results demonstrate that prolonged activation of [alpha]-adrenoceptors in blood vessels leads to downregulation of PKC which may contribute to desensitization of contraction mediated by vasoconstrictors.