title: Intracellular modulation of acid secretion in rat inner medullary collecting duct cells.
abstract: In this study we defined some of the important elements in the acidification process of rat inner medullary collecting duct (IMCD) cells in culture. After cell acidification, i.e., cell pH (pHi) = 6.51 +/- 0.02, pHi increased 0.046 +/- 0.003 units/min. N-ethylmaleimide, N,N'-cyclohexylcarbodiimide, and bafilomycin reduced this rate by over 85%. In contrast, omeprazole and Sch-28080 had no effect. 1,2-Bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid, which prevents a rise in cell Ca2+ concentration ([Ca2+]i) reduced the rate of pHi recovery to 0.013 +/- 0.002 units/min. Calmodulin inhibitors or disruption of cytoskeletal elements with cytochalasin B and colchicine also reduced pHi recovery significantly. In addition, these cells contain acidic vesicles and undergo pHi-regulated endocytosis and exocytosis, which are inhibited by disrupting the cytoskeleton. We conclude that, in our cultured line of rat IMCD cells, proton secretion is mediated by an H(+)-adenosinetriphosphatase. Changes in pHi produce alterations in acid secretion through a signal cascade that requires changes in [Ca2+]i, activation of calmodulin, an intact cytoskeleton, and alteration in the rate of exocytosis and endocytosis.
authors.affiliation: Thorndike Memorial Laboratory, Boston City Hospital, Massachusetts.
authors.forename: J H
authors.initials: JH
authors.lastname: Schwartz
authors.forename: S A
authors.initials: SA
authors.lastname: Masino
authors.forename: R D
authors.initials: RD
authors.lastname: Nichols
authors.forename: E A
authors.initials: EA
authors.lastname: Alexander
mesh_terms: D000143:Acids / Q000378:metabolism*; D000818:Animals; D002118:Calcium; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002614:Chelating Agents / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003599:Cytoskeleton / Q000502:physiology; D004705:Endocytosis; D005089:Exocytosis; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000502:physiology*; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011522:Protons; D051381:Rats
chemical_list: D000143:Acids; D002147:Calmodulin; D002614:Chelating Agents; D011522:Protons; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium