Ionic and secretory response of pancreatic islet cells to minoxidil sulfate.
Minoxidil sulfate is an antihypertensive agent belonging to the new class of vasodilators, the "K+ channel openers." The present study was undertaken to characterize the effects of minoxidil sulfate on ionic and secretory events in rat pancreatic islets. The drug unexpectedly provoked a concentration-dependent decrease in 86Rb outflow. This inhibitory effect was reduced in a concentration-dependent manner by glucose and tolbutamide. Minoxidil sulfate did not affect 45Ca outflow from islets perfused in the presence of extracellular Ca++ and absence or presence of glucose. However, in islets exposed to a medium deprived of extracellular Ca++, the drug provoked a rise in 45Ca outflow. Whether in the absence or presence of extracellular Ca++, minoxidil sulfate increased the cytosolic free Ca++ concentration of islet cells. Lastly, minoxidil sulfate increased the release of insulin from glucose-stimulated pancreatic islets. These results suggest that minoxidil sulfate reduces the activity of the ATP-sensitive K+ channels and promotes an intracellular translocation of Ca++. The latter change might account for the effect of the drug on the insulin-releasing process. However, the secretory response to minoxidil sulfate could also be mediated, at least in part, by a modest Ca++ entry.
Antoine
M H
MH
Laboratory of Pharmacology, Brussels Free University School of Medicine, Belgium.
Hermann
M
M
Herchuelz
A
A
Lebrun
P
P
D000818:Animals; D002132:Calcium Radioisotopes / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008914:Minoxidil / Q000494:pharmacology*; D051381:Rats; D012414:Rubidium Radioisotopes / Q000378:metabolism
D002132:Calcium Radioisotopes; D007328:Insulin; D012414:Rubidium Radioisotopes; D008914:Minoxidil