Purinergic Receptors Stimulate Na+/Ca2+ Exchange in Pancreatic Duct Cells: Possible Role of Proteins Handling and Transporting Ca2+
Most purinergic receptors activate intracellular Ca<sup>2+</sup> signalling, and in epithelia they stimulate transport of major ions. Aim of the present study on pancreatic ducts was to find whether P2 receptors also regulate cellular Ca<sup>2+</sup> transport, such as that via the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (NCX). Since NCX can also be connected with epithelial Ca<sup>2+</sup> transport, we also investigated expression of some Ca<sup>2+</sup>-handling/transporting proteins. Expression analysis revealed that pancreatic ducts of rat and human duct cell line CFPAC-1 (also PANC-1 and Capan-1) express the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (splice variants NCX1.3 and 1.7), as well as the Ca<sup>2+</sup>-sensing receptor and the Ca<sup>2+</sup>-binding protein calbindin-D 9k. These proteins localize to the luminal and lateral membranes of pancreatic duct epithelia. Ca<sup>2+</sup> imaging experiments showed that activation of purinergic P2Y and P2X receptors stimulated NCX in human and rat duct cells. Application of ATP to CFPAC-1 monolayers also stimulated Ca<sup>2+</sup> transport from the luminal to the basolateral side. Taken together, these results show that pancreatic ducts express a number of Ca<sup>2+</sup>-handling/transporting proteins and we propose that these together with purinergic receptors play a role in regulation of duct lumen Ca<sup>2+</sup> content.