Inhibition of ATP-induced surfactant exocytosis by dihydropyridine (DHP) derivatives: a non-stereospecific, photoactivated effect and independent of L-type Ca2+ channels

Purinergic stimulation of surfactant secretion via exocytosis of lamellar b odies is mediated by an elevation of the intracellular Ca2+ concentration ( [Ca2+](i)). We tested the dihydropyridine (DHP) analogues isradipine (+/-en antiomers), nifedipine and Bay K 8644 (racemic forms) an ATP-induced surfac tant secretion and [Ca2+], in single type II cells, using FM1-43 and fura-2 fluorescence. None of the DHPs (2 muM) had an effect on ATP-induced surfac tant secretion in the dark. They did, however, inhibit secretion in a conce ntration-dependent manner during illumination, particularly with W light. T his effect was not stereospecific, because it was mimicked by (-)-isradipin e. In addition, (+)- or (-)-isradipine, but not nifedipine or Bay K 8644, e licited a slow increase of [Ca2+], during illumination with UV light, which was reversible by exposure to dark. None of the DHPs inhibited the ATP-ind uced Ca2+ signal. In perforated patch clamp experiments, depolarizing volta ge steps did not induce L-type Ca2+ (Sr2+) currents, even in the presence o f the agonist Bay K 8644 (1 muM). We conclude that impairment of ATP-induce d surfactant secretion by all tested DHPs and alterations of Ca2+ homeostas is by isradipine are photoactivated effects, independent of L-type Ca2+ cha nnels. (C) 2001 Elsevier Science Inc. All rights reserved.