Evidence for a Na⁺−Ca²⁺ exchanger in rat pancreatic ducts

Abstract

Only recently has it been recognized that intracellular Ca*+ is an important cellular mediator in pancreatic ducts. The aim of the present study was to characterize the Ca2+ efflux pathway in ducts freshly prepared from rat pancreas. Lowering of extracellular Na+ concentration resulted in a significant increase in intracellular Ca '+. This effect was fast, reversible, dependent on the extracellular Na+ concentration and did not correlate with intracellular pH changes. It was abolished in Ca*+-free solutions, indicating that the outwardly directed Na+ gradient was directly coupled to a flufenamate insensitive Ca*+ influx. Removal and reintroduction of extracellular Na+ induced transient hyperpolarization and depolarization of V,,,, respectively. Taken together, our data indicate that pancreatic ducts possess an electrogenic Na+-Ca*+ exchanger, which under control conditions is responsible for transporting Ca*+ out of resting duct cells.

Purinergic Receptors Stimulate Na⁺/Ca^2+ Exchange in Pancreatic Duct Cells: Possible Role of Proteins Handling and Transporting Ca^2+

“…4). We argue that these are specific NCX effects; they are not due to inhibition of Na + /H + exchange and cell acidification [6]; they are not due to influx through flufenamate-sensitive cation channels [20] and the electrophysiological response is consistent with electrogenic NCX [6]. In normal Na -influx mode of NCX transport is now accepted and proposed for other tissues [23][24][25][26].…”

“…Since rat pancreatic ducts express NCX [6,7], we performed key experiments on isolated rat ducts (Fig. 4).…”

“…In addition, NCX may not only be important in regulating intracellular Ca 2+ signalling, but at the organ level it could be a part of transepithelial Ca -ATPase (PMCA) and calcium sensing receptors (CaR) [8][9][10][11]. In pancreas, the normal pancreatic juice contains relatively low Ca 2+ concentrations (<0.5 mM) [12][13][14], but except for a few studies on CaR [15,16] and our studies on NCX [6,7] transport. Present study was performed on rat pancreatic ducts and on cells from human pancreatic duct lines CFPAC-1 (also PANC-1 and Capan-1), which are commonly used as models for epithelial transport of human pancreatic ducts [2].…”

“…However, Ca 2+ signals were inhibited at high nucleotide concentrations, possibly due to unusual stimulation of Ca 2+ efflux. Since rat pancreatic ducts express Na + /Ca 2+ exchanger (NCX1), which is regulated 388 by secretin, acetylcholine and insulin [6,7], it was worth considering whether P2 receptors could regulate this exchanger on a single cell level. In addition, NCX may not only be important in regulating intracellular Ca 2+ signalling, but at the organ level it could be a part of transepithelial Ca -ATPase (PMCA) and calcium sensing receptors (CaR) [8][9][10][11].…”

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

“…Because NTPDase1 is expressed in non-vascular cell types, this finding suggests that NTPDase1 may have functions in the gastrointestinal tract that differ from those demonstrated in the vascular system. (J Histochem Cytochem 52: [861][862][863][864][865][866][867][868][869][870][871]2004) S ince the discovery that adenosine triphosphate (ATP) serves as an extracellular mediator and neurotransmitter, many publications have discussed its role not only in the nervous system but also in other systems, including the gastrointestinal tract (Chan et al 1996;Hug et al 1996;Hede et al 1999;Ishiguro et al 1999). ATP and other extracellular nucleotides influence epithelial cell functions via a variety of P2 receptors (Ralevic and Burnstock 1998).…”