Effects of verapamil and nifedipine on gliclazide-induced increase in cytosolic free Ca2+ in pancreatic islet cells.
The changes in cytosolic free calcium [Ca2+]i induced by the sulfonylurea gliclazide and potassium in normal rat pancreatic islet cells were measured using the fluorescent Ca2+ indicator fura-2. Both in the absence or presence of 5.6 mM glucose, gliclazide caused a rapid and sustained increase in [Ca2+]i. The phenylalkylamine verapamil reduced these increases, but the Ca2+ channel blocker was more potent in the presence than in the absence of glucose. In contrast, nifedipine, a Ca2+ channel blocker of another chemical type, reduced to a similar extent the increase in [Ca2+]i evoked by gliclazide in the absence and presence of glucose. In the absence of glucose, a rise in extracellular K+ concentration from 5 to 20 or 30 mM also induced a rapid and sustained rise in [Ca2+]i. Verapamil more markedly reduced the rise in [Ca2+]i induced by 30 mM than by 20 mM K+. It is concluded that gliclazide increases Ca2+ inflow into normal islet cells primarily, if not exclusively, by opening voltage-sensitive Ca2+ channels. The differential sensitivity toward verapamil of gliclazide-induced rise in [Ca2+]i can be explained by the use-dependent block exerted by Ca2+ channel blockers of the phenylalkylamine type.
Gobbe
P
P
Laboratory of Pharmacology, Brussels University, School of Medicine, Belgium.
Herchuelz
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005907:Gliclazide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D013453:Sulfonylurea Compounds; D014700:Verapamil; D005907:Gliclazide; D009543:Nifedipine; D005947:Glucose; D011188:Potassium; D002118:Calcium