Angiotensin II receptor type I-regulated anion secretion in cystic fibrosis pancreatic duct cells
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AbstractThe beta-adrenergic (cAMP-dependent) regulation of Cl- conductance is defective in cystic fibrosis (CF). The present study explored alternative regulation of anion secretion in CF pancreatic ductal cells (CFPAC-1) by angiotensin II (AII) using the short-circuit current (I-SC technique. An increase in I-SC could be induced in CFPAC-1 cells by basolateral or apical application of AII in a concentration-dependent manner (EC(50) at 3 mu M and 100 mM, respectively). Angiotensin receptor subtypes were identified using specific antagonists, losartan and PD123177, for AT(1) and AT(2) receptors, respectively. It was found that losartan (1 mu M) could completely inhibit the AII-induced I-SC whereas, PD123177 exerted insignificant effect on the I-SC indicating predominant involvement of AT, receptors. The presence of AT(1) receptors in CFPAC-1 cells was also demonstrated by immunohistochemical studies using specific antibodies against AT(1) receptors. Confocal microscopic study demonstrated a rise in intracellular Ca2+ upon stimulation by AII indicating a role of intracellular Ca2+ in mediating the AII response. Depletion of intracellular but not extracellular pool of Ca2+ diminished the AII-induced I-SC. Treatment of the monolayers with a Cl- channel blocker, DIDS, markedly reduced the I-SC indicating that a large portion of the AII-activated I-SC was Cl--dependent. AII-induced I-SC was also observed in monolayers whose basolateral membranes had been permeabilized by nystatin, suggesting that the I-SC was mediated by apical Cl- channels. Our study indicates an AT(1)-mediated Ca2+-dependent regulatory mechanism for anion secretion in CF pancreatic duct cells which may be important for the physiology and pathophysiology of the pancreas.
All Author(s) ListChan HC, Law SH, Leung PS, Fu LXM, Wong PYD
Journal nameJournal of Membrane Biology
Volume Number156
Issue Number3
Pages241 - 249
LanguagesEnglish-United Kingdom
Keywordsangiotensin II; AT(1)-receptor; Ca2+; CFPAC-1 cells; Cl(-)secretion
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Physiology; PHYSIOLOGY

Last updated on 2020-23-10 at 02:02