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 bodies is mediated by an elevation of the intracellular Ca2+ concentration ([Ca2+](i)). We tested the dihydropyridine (DHP) analogues isradipine (+/-enantiomers), nifedipine and Bay K 8644 (racemic forms) on ATP-induced surfactant secretion and [Ca2+](i) in single type II cells, using FM1-43 and fura-2 fluorescence. None of the DHPs (2 microM) had an effect on ATP-induced surfactant secretion in the dark. They did, however, inhibit secretion in a concentration-dependent manner during illumination, particularly with UV light. This effect was not stereospecific, because it was mimicked by (-)-isradipine. In addition, (+)- or (-)-isradipine, but not nifedipine or Bay K 8644, elicited a slow increase of [Ca2+](i) during illumination with UV light, which was reversible by exposure to dark. None of the DHPs inhibited the ATP-induced Ca2+ signal. In perforated patch clamp experiments, depolarizing voltage steps did not induce L-type Ca2+ (Sr(2+)) currents, even in the presence of the agonist Bay K 8644 (1 microM). We conclude that impairment of ATP-induced surfactant secretion by all tested DHPs and alterations of Ca2+ homeostasis by isradipine are photoactivated effects, independent of L-type Ca2+ channels.
Frick
M
M
Department of Physiology, University of Innsbruck, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria.
Siber
G
G
Haller
T
T
Mair
N
N
Dietl
P
P
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism* / Q000502:physiology; D004095:Dihydropyridines / Q000737:chemistry / Q000494:pharmacology*; D004347:Drug Interactions; D005089:Exocytosis / Q000187:drug effects*; D016257:Fura-2 / Q000378:metabolism*; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D008968:Molecular Conformation; D010777:Photochemistry; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000378:metabolism; D013501:Surface-Active Agents / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; C073804:FM1 43; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C038806:1,4-dihydropyridine; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2; D013324:Strontium