Pituitary adenylate-cyclase-activating peptides relax human coronary arteries by activating K-ATP and K-Ca channels in smooth muscle cells
Pituitary adenylate-cyclase-activating peptides relax human coronary arteries by activating K-ATP and K-Ca channels in smooth muscle cells
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DOI：
10.1159/000159197
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发表时间：
1997-01-01
影响因子：
1.7
通讯作者：
Haller, H
中科院分区：
文献类型：
--
作者：
Bruch, L;Bychkov, R;Haller, H
腺苷酸环化酶激活肽（PACAP）是有效的动脉扩张剂，包括人冠状动脉。我们测试的重要性，特定的K+通道的调节机制，在人动脉平滑肌松弛诱导的PACAP，使用收缩和膜片钳测量人冠状动脉血管平滑肌细胞。PACAP 27和PACAP 38产生5 μ M PGF（2 α）-预收缩环的剂量依赖性松弛，分别在1.0 nM和2.0 nM时具有半数最大松弛。两种肽在100 nM时均诱导完全舒张。用ATP依赖性K+（K-ATP）通道阻断剂格列本脲（1 μ M）或钙激活的K+（K-Ca）通道阻断剂伊比利亚毒素（100 nM）预处理血管，以相加方式抑制PACAP 27诱导的舒张。此外，在对来自人冠状动脉的新鲜分离的细胞进行的膜片钳实验中，PACAP 27（100 nM）在一部分细胞中诱导了大的非整流外向（I-K（ATP））K+电流，在其他细胞中诱导了电压依赖性外向（I-K（Ca））K+电流。PACAP 27诱导的I-K（ATP）被格列本脲（3 μ M）阻断，而PACAP 27刺激的I-K（Ca）被伊比利亚毒素（100 nM）阻断。这些发现提供了第一个证据表明，PACAPs舒张动脉平滑肌细胞是通过开放K-ATP和K-Ca通道介导的。结果提示，人血管平滑肌细胞K-ATP和K-Ca通道可能是内源性血管活性信号诱导血管舒张的最终共同通路。
Pituitary adenylate-cyclase-activating peptides (PACAPs) are potent dilators of arteries, including human coronary arteries. We tested the importance of specific K+ channel regulatory mechanisms in human arterial smooth muscle relaxation induced by PACAPs, using contraction and patch clamp measurements on human coronary artery vascular smooth muscle cells. PACAP27 and PACAP38 produced dose-dependent relaxations of 5 mu M PGF(2 alpha)-preconstricted rings, with half-maximal relaxations at 1.0 nM and 2.0 nM, respectively. Both peptides induced complete relaxation at 100 nM. Pretreatment of the vessels with the ATP-dependent K+ (K-ATP) channel blocker glibenclamide (1 mu M) or with the Ca2+-activated K+ (K-Ca) channel blocker iberiotoxin (100 nM) inhibited PACAP27-induced relaxation in an additive manner. Moreover, in the patch clamp experiments on freshly isolated cells from human coronary arteries, PACAP27 (100 nM) induced a large, nonrectifying, outward (I-K(ATP)) K+ current in a proportion of cells and a voltage-dependent outward (I-K(Ca)) K+ current in other cells. The PACAP27-induced I-K(ATP) was blocked by glibenclamide (3 mu M), while the PACAP27-stimulated I-K(Ca) was blocked by iberiotoxin (100 nM). These findings provide the first evidence that relaxation of arterial smooth muscle cells by PACAPs is mediated by opening of K-ATP and K-Ca channels. The data indicate that both K-ATP and K-Ca channels in vascular smooth muscle cells may serve as final common pathway to induce vasorelaxation by endogenous vasoactive signals in man.