The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway

Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway
Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway

Cyclic adenosine diphosphate ribose (cADPR) is a potent endogenous calcium-mobilizing agent synthesized from β-NAD+ by ADP-ribosyl cyclases in sea urchin eggs and in several mammalian cells (Galione, A., and White, A. (1994) Trends Cell Biol. 4, 431-436). Pharmacological studies suggest that cADPR is an endogenous modulator of Ca2+-induced Ca2+ release mediated by ryanodine-sensitive Ca2+ release channels. An unresolved question is whether cADPR can act as a Ca2+-mobilizing intracellular messenger. We show that exogenous application of nitric oxide (NO) mobilizes Ca2+ from intracellular stores in intact sea urchin eggs and that it releases Ca2+ and elevates cADPR levels in egg homogenates. 8-Amino-cADPR, a selective competitive antagonist of cADPR-mediated Ca2+ release, and nicotinamide, an inhibitor of ADP-ribosyl cyclase, inhibit the Ca2+-mobilizing actions of NO, while, heparin, a competitive antagonist of the inositol 1,4,5- trisphosphate receptor, did not affect NO-induced Ca2+ release. Since the Ca2+-mobilizing effects of NO can be mimicked by cGMP, are inhibited by the cGMP-dependent-protein kinase inhibitor, R(p)-8-pCPT-cGMPS, and in egg homogenates show a requirement for the guanylyl cyclase substrate, GTP, we suggest a novel action of NO in mobilizing intracellular calcium from microsomal stores via a signaling pathway involving cGMP and cADPR. These results suggest that cADPR has the capacity to act as a Ca2+-mobilizing intracellular messenger.

0021-9258
3699-3705
Willmott, Nick
b338f44f-ef91-4206-a26e-f9795094d99e
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Walseth, Timothy P.
be22449e-9e3b-4481-b5e5-cde081834855
Lee, Hon Cheung
2bb80b54-c1ff-4692-8256-80804368031f
White, Alison M.
3219cbbd-e1ec-4c77-b5c1-2992ee55b338
Galione, Antony
cb0ece65-6c8a-4c54-9f12-7cd954e0955b
Willmott, Nick
b338f44f-ef91-4206-a26e-f9795094d99e
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Walseth, Timothy P.
be22449e-9e3b-4481-b5e5-cde081834855
Lee, Hon Cheung
2bb80b54-c1ff-4692-8256-80804368031f
White, Alison M.
3219cbbd-e1ec-4c77-b5c1-2992ee55b338
Galione, Antony
cb0ece65-6c8a-4c54-9f12-7cd954e0955b

Willmott, Nick, Sethi, Jaswinder K., Walseth, Timothy P., Lee, Hon Cheung, White, Alison M. and Galione, Antony (1996) Nitric oxide-induced mobilization of intracellular calcium via the cyclic ADP-ribose signaling pathway. The Journal of Biological Chemistry, 271 (7), 3699-3705. (doi:10.1074/jbc.271.7.3699).

Record type: Article

Abstract

Cyclic adenosine diphosphate ribose (cADPR) is a potent endogenous calcium-mobilizing agent synthesized from β-NAD+ by ADP-ribosyl cyclases in sea urchin eggs and in several mammalian cells (Galione, A., and White, A. (1994) Trends Cell Biol. 4, 431-436). Pharmacological studies suggest that cADPR is an endogenous modulator of Ca2+-induced Ca2+ release mediated by ryanodine-sensitive Ca2+ release channels. An unresolved question is whether cADPR can act as a Ca2+-mobilizing intracellular messenger. We show that exogenous application of nitric oxide (NO) mobilizes Ca2+ from intracellular stores in intact sea urchin eggs and that it releases Ca2+ and elevates cADPR levels in egg homogenates. 8-Amino-cADPR, a selective competitive antagonist of cADPR-mediated Ca2+ release, and nicotinamide, an inhibitor of ADP-ribosyl cyclase, inhibit the Ca2+-mobilizing actions of NO, while, heparin, a competitive antagonist of the inositol 1,4,5- trisphosphate receptor, did not affect NO-induced Ca2+ release. Since the Ca2+-mobilizing effects of NO can be mimicked by cGMP, are inhibited by the cGMP-dependent-protein kinase inhibitor, R(p)-8-pCPT-cGMPS, and in egg homogenates show a requirement for the guanylyl cyclase substrate, GTP, we suggest a novel action of NO in mobilizing intracellular calcium from microsomal stores via a signaling pathway involving cGMP and cADPR. These results suggest that cADPR has the capacity to act as a Ca2+-mobilizing intracellular messenger.

This record has no associated files available for download.

More information

Published date: 16 February 1996

Identifiers

Local EPrints ID: 416071
URI: http://eprints.soton.ac.uk/id/eprint/416071
ISSN: 0021-9258
PURE UUID: 337cd00b-f64b-4f27-8b1d-30f9f54d329f
ORCID for Jaswinder K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

Catalogue record

Date deposited: 01 Dec 2017 17:30
Last modified: 10 Nov 2021 03:48

Export record

Altmetrics

Contributors

Author: Nick Willmott
Author: Timothy P. Walseth
Author: Hon Cheung Lee
Author: Alison M. White
Author: Antony Galione

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×