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  • Title: Inhibition of IP3 and IP3-dependent Ca2+ mobilization by cyclic nucleotides in isolated gastric muscle cells.
    Author: Murthy KS, Severi C, Grider JR, Makhlouf GM.
    Journal: Am J Physiol; 1993 May; 264(5 Pt 1):G967-74. PubMed ID: 8388644.
    Abstract:
    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)
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