Similarities between the effects of pinacidil and diazoxide on ionic and secretory events in rat pancreatic islets.
The present study aimed at comparing the effects of pinacidil, a putative K+ channel opener, and diazoxide on ionic and secretory events in rat pancreatic islets. Pinacidil and diazoxide provoked a dose-dependent increase in 86Rb outflow from pancreatic islets perifused in the presence of glucose. Both drugs inhibited the glucose- and tolbutamide-induced increase in 45Ca outflow and insulin release whereas failing to affect the ionic and secretory responses to K+ depolarization. Pinacidil and diazoxide, in contrast to quinine, failed to affect 86Rb outflow from pancreatic islets stimulated by the Ca++-ionophore A23187. Pinacidil as well as diazoxide abolished the glucose-induced increase in [Ca++]i but did not modify the rise in [Ca++]i provoked by KCl. Lastly, both drugs were shown to stimulate an ouabain-resistant modality of 86Rb inflow into the islet cells. The close similarities between the ionic and secretory events mediated by pinacidil and diazoxide suggest that pinacidil could interfere with the same target site as diazoxide; namely the beta-cell ATP-sensitive K+ channel.
Lebrun
P
P
Laboratory of Pharmacology, Brussels Free University School of Medicine, Belgium.
Devreux
V
V
Hermann
M
M
Herchuelz
A
A
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D020110:Pinacidil; D011188:Potassium / Q000502:physiology; D051381:Rats; D012413:Rubidium / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects; D014044:Tolbutamide / Q000494:pharmacology
D006146:Guanidines; D007328:Insulin; D000001:Calcimycin; D020110:Pinacidil; D014044:Tolbutamide; D005947:Glucose; D012413:Rubidium; D003981:Diazoxide; D011188:Potassium; D002118:Calcium