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Nicotinamide inhibits cyclic ADP-ribose-mediated calcium signalling in sea urchin eggs

Nicotinamide inhibits cyclic ADP-ribose-mediated calcium signalling in sea urchin eggs
Nicotinamide inhibits cyclic ADP-ribose-mediated calcium signalling in sea urchin eggs

Cyclic ADP ribose (cADPR) is a potent Ca(2+)-releasing agent, and putative second messenger, the endogenous levels of which are tightly regulated by synthetic (ADP-ribosyl cyclases) and degradative (cADPR hydrolase) enzymes. These enzymes have been characterized in a number of mammalian and invertebrate tissues and their activities are often found on a single polypeptide. beta-NAD+, cGMP and nitric oxide (NO) have been reported to mobilize Ca2+ in the sea urchin egg via the cADPR-mediated pathway. We now report that in sea urchin egg homogenates, nicotinamide inhibits the Ca(2+)-mobilizing action of beta-NAD+, cGMP and NO, but has no effect on cADPR-induced Ca2+ release. Moreover, nicotinamide inhibits cGMP-induced regenerative Ca2+ waves in the intact sea urchin egg. By successfully separating the cADPR-metabolizing machinery from that which releases Ca2+, we have shown that nicotinamide inhibits cADPR-mediated Ca2+ signalling at the level of cADPR generation. Importantly, nicotinamide had no effect upon the hydrolysis of cADPR, and its selective action on cyclase activity was supported by its inhibition of purified Aplysia ADP-ribosyl cyclase, which does not exhibit detectable hydrolytic activity. The action of nicotinamide in blocking Ca2+ release by beta-NAD+, cGMP and NO strongly suggests that these agents act as modulators of cADPR synthesis rather than to sensitize calcium release channels to cADPR.

Adenosine Diphosphate Ribose, Animals, Calcium, Cyclic ADP-Ribose, Microsomes, Niacinamide, Sea Urchins, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't
0264-6021
613-617
Sethi, J.K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Empson, R.M.
8900f024-f907-41ae-ad6d-64d72676546f
Galione, A.
8b37d2a7-fd5a-4666-ac6c-276a9a9ad328
Sethi, J.K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Empson, R.M.
8900f024-f907-41ae-ad6d-64d72676546f
Galione, A.
8b37d2a7-fd5a-4666-ac6c-276a9a9ad328

Sethi, J.K., Empson, R.M. and Galione, A. (1996) Nicotinamide inhibits cyclic ADP-ribose-mediated calcium signalling in sea urchin eggs. Biochemical Journal, 319 (Pt 2), 613-617.

Record type: Article

Abstract

Cyclic ADP ribose (cADPR) is a potent Ca(2+)-releasing agent, and putative second messenger, the endogenous levels of which are tightly regulated by synthetic (ADP-ribosyl cyclases) and degradative (cADPR hydrolase) enzymes. These enzymes have been characterized in a number of mammalian and invertebrate tissues and their activities are often found on a single polypeptide. beta-NAD+, cGMP and nitric oxide (NO) have been reported to mobilize Ca2+ in the sea urchin egg via the cADPR-mediated pathway. We now report that in sea urchin egg homogenates, nicotinamide inhibits the Ca(2+)-mobilizing action of beta-NAD+, cGMP and NO, but has no effect on cADPR-induced Ca2+ release. Moreover, nicotinamide inhibits cGMP-induced regenerative Ca2+ waves in the intact sea urchin egg. By successfully separating the cADPR-metabolizing machinery from that which releases Ca2+, we have shown that nicotinamide inhibits cADPR-mediated Ca2+ signalling at the level of cADPR generation. Importantly, nicotinamide had no effect upon the hydrolysis of cADPR, and its selective action on cyclase activity was supported by its inhibition of purified Aplysia ADP-ribosyl cyclase, which does not exhibit detectable hydrolytic activity. The action of nicotinamide in blocking Ca2+ release by beta-NAD+, cGMP and NO strongly suggests that these agents act as modulators of cADPR synthesis rather than to sensitize calcium release channels to cADPR.

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More information

Published date: 15 October 1996
Keywords: Adenosine Diphosphate Ribose, Animals, Calcium, Cyclic ADP-Ribose, Microsomes, Niacinamide, Sea Urchins, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 422590
URI: https://eprints.soton.ac.uk/id/eprint/422590
ISSN: 0264-6021
PURE UUID: 7180de52-7528-43e1-a030-e8152ea6a8e8
ORCID for J.K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

Catalogue record

Date deposited: 25 Jul 2018 16:30
Last modified: 12 Nov 2019 01:26

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Contributors

Author: J.K. Sethi ORCID iD
Author: R.M. Empson
Author: A. Galione

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