Bell D, McDermott B J
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland, UK.
J Mol Cell Cardiol. 1995 Sep;27(9):1977-87. doi: 10.1016/0022-2828(95)90019-5.
Secretin, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) each exert potent positive contractile responses directly in rat ventricular cardiomyocytes. However, the contractile-coupling mechanisms associated with these responses have not been determined. In the present study, the involvement of L-type calcium channels in the contractile responses elicited by each peptide has been investigated using the selective antagonists at L-type calcium channels, verapamil and diltiazem. Ventricular cardiomyocytes, isolated from the hearts of adult rats, were stimulated to contract at 0.5 Hz in the presence of CaCl2 (2 mM) and adenosine deaminase (5U/ml). Cardiomyocytes were pre-incubated for 3 min prior to stimulation, in the absence of L-type calcium channel antagonist, and in the presence of verapamil (< or = 1 microM) or diltiazem (< or = 1 microM). Verapamil (< or = 1 microM) and diltiazem (< or = 1 microM) inhibited the contractile responses elicited by isoprenaline (100 nM) and forskolin (40 microM), used as positive controls, significantly, and in a concentration-dependent manner, but did not inhibit significantly the contractile response elicited by phenylephrine (2 microM), which was employed as a negative control. Verapamil (< or = 1 microM) and diltiazem (< or = 1 microM) inhibited the contractile responses to secretin (20 nM) and VIP (20 nM) significantly, and in a concentration-dependent manner, but did not inhibit the contractile response to CGRP. These data indicate that the positive contractile responses to secretin and VIP in mammalian ventricular cardiomyocytes involve the influx of calcium ion via L-type calcium channels, while the positive contractile response to CGRP does not.
促胰液素、血管活性肠肽（VIP）和降钙素基因相关肽（CGRP）均可直接对大鼠心室心肌细胞产生强大的正性收缩反应。然而，与这些反应相关的收缩偶联机制尚未明确。在本研究中，使用L型钙通道的选择性拮抗剂维拉帕米和地尔硫䓬，研究了L型钙通道在每种肽引发的收缩反应中的作用。从成年大鼠心脏分离出的心室心肌细胞，在氯化钙（2 mM）和腺苷脱氨酶（5 U/ml）存在的情况下，以0.5 Hz的频率刺激收缩。在不存在L型钙通道拮抗剂、存在维拉帕米（≤1 μM）或地尔硫䓬（≤1 μM）的情况下，心肌细胞在刺激前预孵育3分钟。维拉帕米（≤1 μM）和地尔硫䓬（≤1 μM）显著且呈浓度依赖性地抑制了用作阳性对照的异丙肾上腺素（100 nM）和福斯高林（40 μM）引发的收缩反应，但未显著抑制用作阴性对照的去氧肾上腺素（2 μM）引发的收缩反应。维拉帕米（≤1 μM）和地尔硫䓬（≤1 μM）显著且呈浓度依赖性地抑制了对促胰液素（20 nM）和VIP（20 nM）的收缩反应，但未抑制对CGRP的收缩反应。这些数据表明，哺乳动物心室心肌细胞对促胰液素和VIP的正性收缩反应涉及通过L型钙通道的钙离子内流，而对CGRP的正性收缩反应则不涉及。
