Hilal-Dandan R, Brunton L L
Department of Pharmacology, University of California, San Diego, La Jolla 92093, USA.
Am J Physiol. 1995 Sep;269(3 Pt 2):H798-804. doi: 10.1152/ajpheart.1995.269.3.H798.
We have studied the effect of hyposmotic swelling on adenosin 3',5'-cyclic monophosphate (cAMP) metabolism in isolated cardiac myocytes. Decreasing extracellular osmolarity by 12.5-50% results in graded inhibition (10-40%) of isoproterenol-stimulated and forskolin-stimulated cAMP accumulation but does not affect basal and hormone-stimulated phosphoinositide hydrolysis or cellular ATP content. Treatment with pertussis toxin does not alter the swelling response but abolishes the inhibitory effect of swelling on cAMP accumulation. The response to swelling seems not to involve the release of effectors known to couple to inhibitory G protein (Gi) in myocytes: BQ-123, atropine, and adenosine deaminase do not alter the inhibitory effect of swelling on isoproterenol-stimulated cAMP accumulation; conditioned medium from swollen cells, with restored osmolarity, has no effect on cAMP accumulation when added to control myocytes. In distinction to these effects on myocytes, swelling enhances hormone-stimulated cAMP accumulation in cultured S49 lymphoma cells. We conclude that swelling of cardiac myocytes inhibits cAMP accumulation through a mechanism that involves activation of a pertussis toxin-sensitive Gi protein. Activation of Gi by this means may contribute to adrenergic hyporesponsiveness in hypoxic and ischemic myocardium.
我们研究了低渗肿胀对分离的心肌细胞中3',5'-环磷酸腺苷（cAMP）代谢的影响。将细胞外渗透压降低12.5% - 50%会导致异丙肾上腺素刺激和福斯高林刺激的cAMP积累出现分级抑制（10% - 40%），但不影响基础及激素刺激的磷酸肌醇水解或细胞ATP含量。用百日咳毒素处理不会改变肿胀反应，但会消除肿胀对cAMP积累的抑制作用。对肿胀的反应似乎不涉及已知与心肌细胞中抑制性G蛋白（Gi）偶联的效应物的释放：BQ - 123、阿托品和腺苷脱氨酶不会改变肿胀对异丙肾上腺素刺激的cAMP积累的抑制作用；渗透压恢复后的肿胀细胞条件培养基添加到对照心肌细胞中对cAMP积累没有影响。与对心肌细胞的这些作用不同，肿胀会增强培养的S49淋巴瘤细胞中激素刺激的cAMP积累。我们得出结论，心肌细胞肿胀通过一种涉及激活百日咳毒素敏感的Gi蛋白的机制抑制cAMP积累。通过这种方式激活Gi可能导致缺氧和缺血心肌中的肾上腺素能低反应性。
