cGMP-mediated Ca2+ release from IP3-insensitive Ca2+ stores in smooth muscle.
cGMP-mediated Ca2+ release from IP3-insensitive Ca2+ stores in smooth muscle.
复制标题
cGMP 介导的平滑肌中 IP3 不敏感 Ca2 储存的 Ca2 释放。
DOI：
10.1152/ajpcell.1998.274.5.c1199
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Makhlouf,GM
中科院分区：
文献类型：
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作者：
Murthy,KS;Makhlouf,GM
最近关于一氧化氮（NO）在胃肠道平滑肌中的作用的研究提出了NO刺激的cGMP可能在缺乏cGMP依赖性蛋白激酶（PKG）活性的情况下作为Ca2+动员信使的可能性[K]。S. Murthy, k.m。张,J.-G。金，J. T.格莱德，和G. M.马克鲁。[j] .生理学杂志。肝脏生理杂志，28(2):669 - 671,1993]。这一观点在分散的8-溴-cGMP （8-BrcGMP）和NO和血管活性肠肽（VIP）的胃平滑肌细胞中进行了检验，这些细胞可以刺激内源性cGMP。在camp依赖性蛋白激酶（PKA）和PKG抑制剂（H-89和KT-5823）处理的肌肉细胞中，8-BrcGMP （10 μM）、NO （1 μM）和VIP （1 μM）刺激45ca2 +释放（45ca2 +细胞含量降低21±3 ~ 30±1%）；8-BrcGMP刺激Ca2+释放呈浓度依赖性，ec50为0.4±0.1 μM，阈值为10 nM。8-BrcGMP和NO增加胞质游离Ca2+浓度（[Ca2+]i）并诱导收缩；这两种反应在Ca2+储存被thapsigarin耗尽后被消除。VIP通常通过刺激Ca2+内流而增加[Ca2+] ii，用PKA和PKG抑制剂治疗导致[Ca2+] ii进一步增加，在用thapsigargin预处理的细胞中恢复到控制水平。肝素和钌红对通透性肌细胞中cGMP和NO诱导的Ca2+释放和收缩均无影响。cGMP和肌醇1,4,5-三磷酸（IP3）的最有效浓度诱导的Ca2+释放是添加剂，与先施用哪种药物无关。我们得出结论，在缺乏PKA和PKG活性的情况下，cGMP刺激Ca2+从IP3不敏感的储存中释放出来，并且其作用与IP3的作用是附加的。
Recent studies on the role of nitric oxide (NO) in gastrointestinal smooth muscle have raised the possibility that NO-stimulated cGMP could, in the absence of cGMP-dependent protein kinase (PKG) activity, act as a Ca2+-mobilizing messenger [K. S. Murthy, K.-M. Zhang, J.-G. Jin, J. T. Grider, and G. M. Makhlouf.Am. J. Physiol.265 (Gastrointest. Liver Physiol.28): G660–G671, 1993]. This notion was examined in dispersed gastric smooth muscle cells with 8-bromo-cGMP (8-BrcGMP) and with NO and vasoactive intestinal peptide (VIP), which stimulate endogenous cGMP. In muscle cells treated with cAMP-dependent protein kinase (PKA) and PKG inhibitors (H-89 and KT-5823), 8-BrcGMP (10 μM), NO (1 μM), and VIP (1 μM) stimulated45Ca2+release (21 ± 3 to 30 ± 1% decrease in45Ca2+cell content); Ca2+release stimulated by 8-BrcGMP was concentration dependent with an EC50of 0.4 ± 0.1 μM and a threshold of 10 nM. 8-BrcGMP and NO increased cytosolic free Ca2+concentration ([Ca2+]i) and induced contraction; both responses were abolished after Ca2+stores were depleted with thapsigargin. With VIP, which normally increases [Ca2+]iby stimulating Ca2+influx, treatment with PKA and PKG inhibitors caused a further increase in [Ca2+]ithat reverted to control levels in cells pretreated with thapsigargin. Neither Ca2+release nor contraction induced by cGMP and NO in permeabilized muscle cells was affected by heparin or ruthenium red. Ca2+release induced by maximally effective concentrations of cGMP and inositol 1,4,5-trisphosphate (IP3) was additive, independent of which agent was applied first. We conclude that, in the absence of PKA and PKG activity, cGMP stimulates Ca2+release from an IP3-insensitive store and that its effect is additive to that of IP3.