The Mechanism of Muscarinic Agonist-Stimulated Inositol Phosphate Formation in Permeabilized Ileal Smooth Muscle.
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Muscarinic agonists and guanylyl-5''-imidodiphosphate (Gpp(NH)p) stimulated formation of inositol phosphates in permeabilized longitudinal smooth muscle of guinea pig ileum. Gpp(NH)p markedly potentiated the formation of inositol bisphosphate (IP<SUB>2</SUB>) and inositol trisphosphate (IP<SUB>3</SUB>) stimulated by carbachol, but increased inositol monophosphate formation (IP<SUB>1</SUB>) only slightly. Gpp(NH)p enhanced the formation of IP<SUB>2</SUB> + IP<SUB>3</SUB> induced by either acetylcholine or carbachol about fourfold in a synergistic manner, but enhanced the effects of oxotremorine and pilocarpine less than twofold in an additive manner. Elevation of Ca<SUB>2+</SUB> concentration resulted in increases of the inositol phosphate levels stimulated by both carbachol and Gpp(NH)p. The optimal concentration of Ca<SUB>2+</SUB> for carbachol-stimulated formations of IP<SUB>2</SUB> + IP<SUB>3</SUB> was shifted to a lower Ca<SUB>2+</SUB> concentration in the presence of Gpp(NH)p. These findings suggest that muscarinic receptor-stimulated polyphosphoinositide hydrolysis in ileal smooth muscle results in inositol polyphosphate formation via GTP binding protein (G-protein). The muscarinic receptor-activated G-protein decreases the Ca<SUB>2+</SUB> requirement of polyphosphoinositide hydrolysis. Muscarinic agonists stimulate inositol polyphosphate formation by interaction of the G-protein activation of a phosphoinositide specific phospholipase C with Ca<SUB>2+</SUB> influx.
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- The Mechanism of Muscarinic Agonist-Stimulated Inositol Phosphate Formation in Permeabilized Ileal Smooth Muscle.