Does the hydrolysis of inositol phospholipids lead to the opening of voltage operated Ca2+ channels in guinea-pig ileum? Studies with fluoride ions and caffeine.
Fluoride ions (1-30 mM) stimulate phosphoinositide hydrolysis in guinea-pig ileum longitudinal smooth muscle slices, and this is not inhibited in the presence of indomethacin or nifedipine. This action is associated with a slow contractile response which peaks after approximately five minutes and then declines towards baseline; at this time the contractile response to a maximally effective concentration of carbachol is also inhibited. Fluoride-induced contractions are inhibited completely in the presence of nifedipine. Similarly, contractions induced by caffeine, which releases Ca2+ from intracellular stores, are also inhibited by nifedipine. These data are consistent with a model in which the activation of a G-protein by F- ions leads to the following sequential events: activation of phospholipase C, release of intracellular Ca2+, opening of voltage operated (i.e. dihydropyridine sensitive) Ca2+ channels and contraction. The transient nature of the fluoride contraction and the inhibition of the carbachol contraction may be due to a slow elevation of cAMP levels induced by F-.
Watson
S P
SP
Department of Pharmacology, University of Oxford.
Stanley
A F
AF
Sasaguri
T
T
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*
D010716:Phosphatidylinositols; D005576:Colforsin; D002110:Caffeine; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol; D005459:Fluorides; D002118:Calcium