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.