AJP - Renal Physiology, Vol 263, Issue 4 749-F756, Copyright © 1992 by American Physiological Society

ARTICLES

Adaptation of rabbit cortical collecting duct to in vitro acid incubation

K. Yasoshima, L. M. Satlin and G. J. Schwartz
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461.

Cortical collecting ducts (CCDs) isolated from acid-loaded rabbits and perfused in vitro absorb HCO3-, whereas CCDs from normal animals secrete HCO3-. We have previously shown that CCDs incubated in vitro for 3 h at pH 6.9 show a reduction in net (baseline and stimulated) HCO3- secretion. In this study we ascertained the minimum duration of an acidic stimulus necessary to induce adaptive changes in stimulated HCO3- secretion (determined in the absence of basolateral Cl-) and the roles of protein synthesis and cytoskeletal function in this process. CCDs incubated in acid (pH 6.8, HCO3- 6 mM) for 1 h followed by incubation at pH 7.4 (HCO3- 25 mM) for 2 h showed a 41% reduction in stimulated HCO3- secretion (P < 0.001), similar to that observed after 3 h of incubation at pH 6.8. However, this incubation protocol failed to enhance stimulated HCO3- absorption (determined in the absence of luminal Cl-). Addition of 10 microM anisomycin, a reversible inhibitor of protein synthesis, throughout the entire period of incubation (1 h at pH 6.8 plus 2 h at pH 7.4) blocked adaptive reduction in HCO3- secretion, as did exposure to anisomycin only during the initial 1 h of acid incubation. In contrast, anisomycin application during the 2-h incubation at pH 7.4 failed to block this adaptation of HCO3- secretion. Application of 4 microM actinomycin D, an inhibitor of DNA transcription, during the acid incubation also prevented the adaptive response, as did application during the total or during the 2-h pH 7.4 incubation period of 0.2 microM cytochalasin D, an inhibitor of actin filament function.(ABSTRACT TRUNCATED AT 250 WORDS)

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