Two different but converging messenger pathways to intracellular Ca2+ release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate

Cansela, Jose Manuel, Gerasimenko, Oleg Vsevolodovich ORCID: https://orcid.org/0000-0003-2573-8258, Gerasimenko, Julia Vladimirovna ORCID: https://orcid.org/0000-0002-2262-2543, Tepikin, Alexei V. and Petersen, Ole Holger ORCID: https://orcid.org/0000-0002-6998-0380 2000. Two different but converging messenger pathways to intracellular Ca2+ release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate. Embo Journal 19 (11) , pp. 2549-2557. 10.1093/emboj/19.11.2549

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Abstract

Hormones and neurotransmitters mobilize Ca2+ from the endoplasmic reticulum via inositol trisphosphate (IP3) receptors, but how a single target cell encodes different extracellular signals to generate specific cytosolic Ca2+ responses is unknown. In pancreatic acinar cells, acetylcholine evokes local Ca2+ spiking in the apical granular pole, whereas cholecystokinin elicits a mixture of local and global cytosolic Ca2+ signals. We show that IP3, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP) evoke cytosolic Ca2+ spiking by activating common oscillator units composed of IP3 and ryanodine receptors. Acetylcholine activation of these common oscillator units is triggered via IP3 receptors, whereas cholecystokinin responses are triggered via a different but converging pathway with NAADP and cyclic ADP-ribose receptors. Cholecystokinin potentiates the response to acetylcholine, making it global rather than local, an effect mediated specifically by cyclic ADP-ribose receptors. In the apical pole there is a common early activation site for Ca2+ release, indicating that the three types of Ca2+ release channels are clustered together and that the appropriate receptors are selected at the earliest step of signal generation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences Research Institutes & Centres > Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology
Publisher:	Nature Publishing Group
ISSN:	0261-4189
Last Modified:	28 Oct 2022 08:29
URI:	https://orca.cardiff.ac.uk/id/eprint/71002

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