Muscarinic receptors stimulate Ca2+ influx via phospholipase A2 pathway in ileal smooth muscles.
Receptor-mediated changes in intracellular Ca2+ in ileal longitudinal smooth muscles of guinea pig were studied. Stimulation of muscarinic receptors by carbachol induced both Ca(2+)-influx through plasma membranes and Ca(2+)-release from intracellular stores. Pretreatment of the muscle with an inhibitor of phospholipase A2 abolished the Ca2+ influx but not the Ca(2+)-release, whereas an inhibitor of phospholipase C showed opposite effects. The inhibitors of cyclooxygenase and lipoxygenase enhanced the muscarinic receptor-induced Ca(2+)-influx. Addition of arachidonic acid mimic the receptor-induced Ca(2+)-influx. Treatment of muscles with pertussis toxin abolished the receptor-induced release of arachidonic acid as well as Ca(2+)-influx, but was less effective on the IP3 formation and the Ca(2+)-release. Taken together, our results suggest that phospholipase A2 but not phospholipase C pathway is involved in the muscarinic receptor-induced Ca(2+)-influx in ileal smooth muscle.
Department of Pharmacology, Osaka University School of Medicine, Japan.
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Wang
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Osugi
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Uchida
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D009130:Muscle, Smooth / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D047309:Flavones
D016718:Arachidonic Acid; D002118:Calcium; D002217:Carbachol; D005419:Flavonoids; D005456:Fluorescent Dyes; D016257:Fura-2; D007202:Indicators and Reagents; D015759:Ionomycin; D009355:Neomycin; D010741:Phospholipases A; D054467:Phospholipases A2; D011976:Receptors, Muscarinic; D010738:Type C Phospholipases; C049925:fura-2-am; C008548:morin; D047309:Flavones