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Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology

Gryshchenko, Oleksiy, Gerasimenko, Julia V., Peng, Shuang, Gerasimenko, Oleg V. and Petersen, Ole Holger 2018. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology. Journal of Physiology 596 (14) , pp. 2663-2678. 10.1113/JP275395

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Abstract

Physiological Ca2+ signals in pancreatic acinar cells control fluid and enzyme secretion, whereas excessive Ca2+ signals induced by pathological agents induce destructive processes leading to acute pancreatitis. Ca2+ signals in the periacinar stellate cells may also play a role in the development of acute pancreatitis. In this study, we have explored Ca2+ signalling in the different cell types to be found in the acinar environment of the pancreatic tissue. We have, for the first time, recorded depolarization-evoked Ca2+ signals in pancreatic nerves and shown that whereas acinar cells receive a functional cholinergic innervation, there is no evidence for functional innervation of the stellate cells. The stellate, like the acinar, cells are not electrically excitable as they do not generate Ca2+ signals in response to membrane depolarization. The principal agent evoking Ca2+ signals in the stellate cells is bradykinin, but in experimental alcohol-related acute pancreatitis, these cells become much less responsive to bradykinin and then acquire sensitivity to trypsin. Our new findings have implications for our understanding of the development of acute pancreatitis and we propose a scheme in which Ca2+ signals in stellate cells provide an amplification loop promoting acinar cell death. Initial release of the proteases kallikrein and trypsin from dying acinar cells can, via bradykinin generation and protease activated receptors, induce Ca2+ signals in stellate cells which can then, possibly via nitric oxide generation, damage more acinar cells and thereby cause additional release of proteases, generating a vicious circle.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Publisher: Wiley
ISSN: 0022-3751
Date of First Compliant Deposit: 1 February 2018
Date of Acceptance: 25 January 2018
Last Modified: 29 Jan 2019 22:09
URI: http://orca.cf.ac.uk/id/eprint/108706

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