title: Verapamil: a novel probe of surfactant secretion from rat type II pneumocytes.
abstract: Surfactant from type II pneumocytes prevents the alveolar atelectasis found in both the neonatal and adult forms of respiratory distress syndrome. We have found that verapamil, a phenylalkene with calcium channel and alpha 1-receptor binding properties, has a multiphasic concentration effect on surfactant secretion from [3H]choline-labeled rat type II pneumocytes in culture. Verapamil (10(-8) M) caused a 24% stimulation of surfactant secretion, whereas an 8% inhibition was found at 10(-6) M and a 70% stimulation was found at 10(-4) M. Lactate dehydrogenase release occurred at 5 x 10(-4) M verapamil. Verapamil (10(-4) M) also produced a 100% increase in adenosine 3',5'-cyclic monophosphate (cAMP) in comparison with concentrations of less than or equal to 10(-6) M, an effect that could not be blocked by propranolol (10(-4) M). Verapamil (10(-6) M) increased the total formation of inositol phosphates (IP) by 23% in comparison with IP formation in control cells. Calcium influx was inhibited 15% by 10(-8) M verapamil and 37% by 10(-4) M verapamil. Calcium efflux was stimulated 44% by 10(-5) M verapamil. In combination with 50% effective concentrations (EC50) of terbutaline, phorbol ester, and ATP, the respective effects of verapamil (10(-4) M) on surfactant secretion were approximately additive. We conclude that verapamil has a novel multiphasic concentration effect on surfactant secretion, which appears to involve several signal transduction pathways including cAMP formation, IP formation, inhibition of calcium influx, and stimulation of calcium efflux.
authors.affiliation: Department of Pediatrics, University of Southern California School of Medicine, Children's Hospital of Los Angeles 90054.
authors.forename: D
authors.initials: D
authors.lastname: Warburton
authors.forename: L
authors.initials: L
authors.lastname: Parton
authors.forename: S
authors.initials: S
authors.lastname: Buckley
authors.forename: L
authors.initials: L
authors.lastname: Cosico
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000302:isolation & purification / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D013726:Terbutaline / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D007295:Inositol Phosphates; D010743:Phospholipids; D011663:Pulmonary Surfactants; D000255:Adenosine Triphosphate; D014700:Verapamil; D007770:L-Lactate Dehydrogenase; D013726:Terbutaline; D002794:Choline; D013755:Tetradecanoylphorbol Acetate