Different pathways for Ca2+ influx and intracellular release of Ca2+ mediated by muscarinic receptors in ileal longitudinal smooth muscle.
Muscarinic receptor-mediated elevations in intracellular Ca2+ concentration ([Ca2+]i) in the longitudinal smooth muscle of guinea pig ileum were studied by the use of fura-2 fluorescence. Dose-response analysis indicated a difference in the potencies of carbachol (CCh) to increase [Ca2+]i in the presence and absence of extracellular Ca2+. For the increase in [Ca2+]i due to Ca2+ release from intracellular stores in the absence of extracellular Ca2+, the ED50 value of CCh was 3 x 10(-5) M. On the other hand, in the presence of Ca2+, the ED50 value was 2.5 x 10(-7) M, indicating that a low concentration of CCh (less than 10(-7) M) caused influx of extracellular Ca2+ without Ca2+ release. Oxotremorine and pilocarpine induced Ca2+ influx, but were less potent inducers of Ca2+ release. CCh also stimulated the formation of inositol trisphosphates (IP3) with an ED50 value of (4.5 x 10(-5) M), which was similar to that for Ca2+ release from intracellular stores. Treatment of the smooth muscle with neomycin (1 mM), a phospholipase C inhibitor, abolished both CCh-induced IP3 formation and Ca2+ release from intracellular stores, but did not affect CCh-induced Ca2+ influx. These results suggest that the pathway for muscarinic stimulation of Ca2+ influx through plasma membranes is different from that for Ca2+ release from intracellular stores, which seems to be coupled with IP3 formation.
Wang
X B
XB
Department of Pharmacology I, Osaka University School of Medicine, Japan.
Osugi
T
T
Uchida
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000032:analysis; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D010277:Parasympathomimetics / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D014316:Tritium
D007295:Inositol Phosphates; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D014316:Tritium; D002118:Calcium