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.
Department of Pharmacology, Oxford.
S P
SP
Watson
J
J
Lai
T
T
Sasaguri
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D020960:omega-Conotoxins
D008978:Mollusk Venoms; D010716:Phosphatidylinositols; D012604:Scorpion Venoms; D015222:Sodium Channels; D020960:omega-Conotoxins; C053423:Conus magus toxin; D013373:Substance P; D013779:Tetrodotoxin; D004533:Egtazic Acid; D002217:Carbachol; D009543:Nifedipine; D011188:Potassium; D002118:Calcium