Ca2+ signals mediated by bradykinin type 2 receptors in normal pancreatic stellate cells can be inhibited by specific Ca2+ channel blockade

Gryshchenko, Oleksiy, Gerasimenko, Julia V. ORCID: https://orcid.org/0000-0002-2262-2543, Gerasimenko, Oleg V. ORCID: https://orcid.org/0000-0003-2573-8258 and Petersen, Ole H. ORCID: https://orcid.org/0000-0002-6998-0380 2016. Ca2+ signals mediated by bradykinin type 2 receptors in normal pancreatic stellate cells can be inhibited by specific Ca2+ channel blockade. Journal of Physiology 594 (2) , pp. 281-293. 10.1113/JP271468

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Abstract

Normal pancreatic stellate cells (PSCs) are regarded as quiescent, only to become activated in chronic pancreatitis and pancreatic cancer. However, we now report that these cells in their normal microenvironment are far from quiescent, but are capable of generating substantial Ca2+ signals. We have compared Ca2+ signalling in PSCs and their better studied neighbouring acinar cells (PACs) and found complete separation of Ca2+ signalling in even closely neighbouring PACs and PSCs. Bradykinin (BK), at concentrations corresponding to the slightly elevated plasma BK levels that have been shown to occur in the auto-digestive disease acute pancreatitis in vivo, consistently elicited substantial Ca2+ signals in PSCs, but never in neighbouring PACs, whereas the physiological PAC stimulant cholecystokinin failed to evoke Ca2+ signals in PSCs. The BK-induced Ca2+ signals were mediated by B2 receptors and B2 receptor blockade protected against PAC necrosis evoked by agents causing acute pancreatitis. The initial Ca2+ rise in PSCs was due to inositol trisphosphate receptor-mediated release from internal stores, whereas the sustained phase depended on external Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels. CRAC channel inhibitors, which have been shown to protect PACs against damage caused by agents inducing pancreatitis, therefore also inhibit Ca2+ signal generation in PSCs and this may be helpful in treating acute pancreatitis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher:	Wiley
ISSN:	0022-3751
Funders:	MRC
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	30 September 2015
Last Modified:	02 May 2023 20:52
URI:	https://orca.cardiff.ac.uk/id/eprint/80833

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