K(+)-stimulation of the phosphoinositide pathway in guinea-pig ileum longitudinal smooth muscle is predominantly neuronal in origin and mediated by the entry of extracellular Ca2+.

1. K+ and scorpion toxin stimulate formation of inositol phosphates in guinea-pig ileum longitudinal smooth muscle slices. The response to these two agents is not additive. 2. The response to K+ is inhibited partially by nifedipine and partially by omega-conotoxin. When given together the effect of these two Ca2+ channel blockers is additive and the response to K+ is reduced by more than 80%. 3. The response to scorpion toxin is inhibited completely by tetrodotoxin, partially by omega-conotoxin but not by atropine or nifedipine. Scorpion toxin induces a similar formation of inositol phosphates in collagenase-dispersed cells to that seen in cross-chopped slices. 4. The responses to scorpion toxin and K+ are inhibited completely when the extracellular Ca2+ concentration is reduced to below cytosolic levels (less than 100 nM). 5. Neither nifedipine nor omega-conotoxin, either alone or in combination, inhibited formation of inositol phosphates by substance P or carbachol. Both of these agonists induced a significant formation of inositol phosphates even when the extracellular Ca2+ concentration was reduced to 10 nM. 6. These results indicate that K+ and scorpion toxin induce formation of inositol phosphates through the mobilisation of extracellular Ca2+. The response to K+ appears to occur predominantly in neuronal cells.