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

Most purinergic receptors activate intracellular Ca(2+) 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(2+) transport, such as that via the Na(+)/Ca(2+) exchanger (NCX). Since NCX can also be connected with epithelial Ca(2+) transport, we also investigated expression of some Ca(2+)-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(+)/Ca(2+) exchanger (splice variants NCX1.3 and 1.7), as well as the Ca(2+)-sensing receptor and the Ca(2+)-binding protein calbindin-D 9k. These proteins localize to the luminal and lateral membranes of pancreatic duct epithelia. Ca(2+) 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(2+) transport from the luminal to the basolateral side. Taken together, these results show that pancreatic ducts express a number of Ca(2+)-handling/transporting proteins and we propose that these together with purinergic receptors play a role in regulation of duct lumen Ca(2+) content.