Murthy K S, Severi C, Grider J R, Makhlouf G M
Department of Medicine, Medical College of Virginia, Richmond 23298.
Am J Physiol. 1993 May;264(5 Pt 1):G967-74. doi: 10.1152/ajpgi.1993.264.5.G967.
The mechanisms by which cAMP and cGMP and agents that stimulate one (isoproterenol and nitroprusside) or both cyclic nucleotides (VIP) decrease cytosolic free Ca2+ ([Ca2+]i) and inhibit contraction were examined in dispersed, intact, and saponin-permeabilized gastric muscle cells. In these cells, the [Ca2+]i transient responsible for initial contraction is mediated by inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release (K. N. Bitar, P. G. Bradford, J. W. Putney, Jr., and G. M. Makhlouf, Science Wash. DC 232: 1143-1145, 1986, and J. Biol. Chem. 261: 16591-16596, 1986). In intact muscle cells, dibutyryl cAMP and all three relaxant agents inhibited contraction, [Ca2+]i, and net Ca2+ efflux (i.e., Ca2+ release) in a concentration-dependent fashion. In permeabilized muscle cells, cAMP, cGMP, and all three relaxant agents 1) inhibited cholecystokinin (CCK)-induced IP3 production (maximal 38-48%), 2) inhibited CCK- and IP3-induced Ca2+ efflux (maximal 55-59%) and contraction (maximal 59-66%), and 3) stimulated Ca2+ uptake (maximal 25-30%), in a concentration-dependent fashion. cAMP and cGMP were equipotent inhibitors of IP3 production and of CCK- and IP3-induced Ca2+ efflux and contraction, whereas cGMP was distinctly more potent as a stimulant of Ca2+ uptake. For all functions, maximal effects induced by cAMP and cGMP were similar to those induced by the three relaxant agents. Inhibition of Ca2+ release was the main determinant of inhibition of contraction; stimulation of Ca2+ uptake was relatively minor (< 5% of Ca2+ efflux). Decrease in IP3 production did not contribute to inhibition of Ca2+ efflux and contraction since inhibition of IP3-induced Ca2+ efflux was similar to inhibition of CCK-induced IP3-dependent Ca2+ efflux.(ABSTRACT TRUNCATED AT 250 WORDS)
在分散的、完整的和皂角苷通透的胃肌细胞中，研究了环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）以及刺激一种（异丙肾上腺素和硝普钠）或两种环核苷酸（血管活性肠肽）降低胞质游离钙离子浓度（[Ca2+]i）并抑制收缩的机制。在这些细胞中，负责初始收缩的[Ca2+]i瞬变由1,4,5-三磷酸肌醇（IP3）依赖性钙离子释放介导（K.N.比塔尔、P.G.布拉德福德、J.W.普特尼和G.M.马克洛夫，《科学》华盛顿特区232:1143 - 1145,1986年，以及《生物化学杂志》261:16591 - 16596,1986年）。在完整的肌细胞中，二丁酰cAMP和所有三种松弛剂均以浓度依赖性方式抑制收缩、[Ca2+]i和净钙离子外流（即钙离子释放）。在通透的肌细胞中，cAMP、cGMP和所有三种松弛剂1）抑制胆囊收缩素（CCK）诱导的IP3生成（最大抑制率38 - 48%），2）抑制CCK和IP3诱导的钙离子外流（最大抑制率55 - 59%）和收缩（最大抑制率59 - 66%），3）以浓度依赖性方式刺激钙离子摄取（最大刺激率25 - 30%）。cAMP和cGMP对IP3生成以及CCK和IP3诱导的钙离子外流和收缩的抑制作用相当，而cGMP作为钙离子摄取刺激剂的作用明显更强。对于所有功能，cAMP和cGMP诱导的最大效应与三种松弛剂诱导的效应相似。抑制钙离子释放是抑制收缩的主要决定因素；刺激钙离子摄取的作用相对较小（<钙离子外流的5%）。IP3生成的减少对钙离子外流和收缩的抑制作用无贡献，因为抑制IP3诱导的钙离子外流与抑制CCK诱导的IP3依赖性钙离子外流相似。（摘要截短于250字）
