Effects of cyclosporin A on induced HIT cell alkalinization.
We studied whether therapeutic doses of cyclosporin A (CsA) modify the effects of nutrient and non-nutrient stimuli on pHi, in the insulin-secreting beta-cell line HIT-T15. Glucose caused a transient acidification, followed by alkalinization. CsA failed to block this alkalinization. PMA elicited a gradual alkalinization by a protein kinase C mediated mechanism which is not inhibited by CsA. The depolarization with high K+ was associated with a rise in pHi. CsA was able to completely block this increase in pHi. Ionomycin induced a rapid cytosolic alkalinization partially inhibited by CsA. We conclude that in HIT-T15 cells, therapeutical doses of CsA inhibit the Ca(2+)-dependent pathway of Na+/H+ antiport activation but not protein kinase C activation of this exchanger.
Martin
F
F
Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, Spain.
Trebilcock
R
R
Best
L
L
D000818:Animals; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D015759:Ionomycin / Q000037:antagonists & inhibitors; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015759:Ionomycin; D011189:Potassium Chloride; D016572:Cyclosporine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate