Purinergic regulation of anion secretion by cystic fibrosis pancreatic duct cells
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AbstractThe present study explored regulation of anion secretion across cystic fibrosis pancreatic ductal epithelium by extracellular ATP with the short-circuit current (I-sc) technique. CFPAC-1 cells grown on Millipore filters formed polarized monolayers with junctional complexes as revealed by light and electron microscopy. The cultured monolayers exhibited an increase in I-sc in response to apical application of ATP in a concentration-dependent manner (concentration eliciting 50% of maximal response = 3 mu M). Replacement of Cl- in the bathing solution or treatment of the cells with a Cl- channel blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), markedly reduced I-sc, indicating that a substantial portion of ATP-activated I-sc was Cl- dependent. The effects of different adenosine nucleosides and/or nucleotides on I-sc were also studied to identify the type of purinoceptors involved. The order of potency, ATP = UTP > ADP > adenosine, was consistent with that for P-2 purinoceptors. Reactive blue 2 (100 mu M), a P-2 antagonist, was found to inhibit 86% of ATP-induced I-sc. ATP-induced I-sc was also inhibited by pretreatment of the cells with a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (50 mu M) Confocal microscopic study also demonstrated a rise in intracellular Ca2+ with stimulation by extracellular ATP, indicating a role of intracellular Ca2+ in mediating the ATP response. ATP-induced I-sc was observed in monolayers whose basolateral membranes had been permeabilized by nystatin, which was also sensitive to apical addition of DIDS, suggesting that I-sc was mediated by apical Cl- channels. The results of the present study demonstrate the presence of a purinergic regulatory mechanism involving P-2u receptor and Ca2+ mobilization in pancreatic duct anion secretion.
All Author(s) ListChan HC, Cheung WT, Leung PY, Wu LJ, Chew SBC, Ko WH, Wong PYD
Journal nameAmerican Journal of Physiology - Cell Physiology
Volume Number271
Issue Number2
PagesC469 - C477
LanguagesEnglish-United Kingdom
Keywordsadenosine 5'-triphosphate; calcium; P-2 purinoceptor; pancreatic duct cells
Web of Science Subject CategoriesCell Biology; CELL BIOLOGY; Physiology; PHYSIOLOGY

Last updated on 2021-25-01 at 02:05