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 effecive 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^-.