QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 9 September 2003
doi: 10.1242/jcs.00713

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.00713v1 116/21/4291    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bradley, K. N. Articles by McCarron, J. G. Search for Related Content PubMed PubMed Citation Articles by Bradley, K. N. Articles by McCarron, J. G. Social Bookmarking                         What's this?

Cyclic ADP-ribose increases Ca²⁺ removal in smooth muscle

Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK

^* Author for correspondence (e-mail: j.mccarron{at}bio.gla.ac.uk)

Accepted 17 June 2003

Ca²⁺ release via ryanodine receptors (RyRs) is vital in cell signalling and regulates diverse activities such as gene expression and excitation-contraction coupling. Cyclic ADP ribose (cADPR), a proposed modulator of RyR activity, releases Ca²⁺ from the intracellular store in sea urchin eggs but its mechanism of action in other cell types is controversial. In this study, caged cADPR was used to examine the effect of cADPR on Ca²⁺ signalling in single voltage-clamped smooth muscle cells that have RyR but lack FKBP12.6, a proposed target for cADPR. Although cADPR released Ca²⁺ in sea urchin eggs (a positive control), it failed to alter global or subsarcolemma [Ca²⁺]_c, to cause Ca²⁺-induced Ca²⁺ release or to enhance caffeine responses in colonic myocytes. By contrast, caffeine (an accepted modulator of RyR) was effective in these respects. The lack of cADPR activity on Ca²⁺ release was unaffected by the introduction of recombinant FKBP12.6 into the myocytes. Indeed in western blots, using brain membrane preparations as a source of FKBP12.6, cADPR did not bind to FKBPs, although FK506 was effective. However, cADPR increased and its antagonist 8-bromo-cADPR slowed the rate of Ca²⁺ removal from the cytoplasm. The evidence indicates that cADPR modulates [Ca²⁺]_c but not via RyR; the mechanism may involve the sarcolemma Ca²⁺ pump.

Key words: cADPR, FKBPs, Ca²⁺ pumps, Ca²⁺ signalling, Ryanodine receptors

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Wray and T. Burdyga Sarcoplasmic Reticulum Function in Smooth Muscle Physiol Rev, January 1, 2010; 90(1): 113 - 178. [Abstract] [Full Text] [PDF]

				M. J. Berridge Smooth muscle cell calcium activation mechanisms J. Physiol., November 1, 2008; 586(21): 5047 - 5061. [Abstract] [Full Text] [PDF]

				N. Fritz, N. Macrez, J. Mironneau, L. H. Jeyakumar, S. Fleischer, and J.-L. Morel Ryanodine receptor subtype 2 encodes Ca2+ oscillations activated by acetylcholine via the M2 muscarinic receptor/cADP-ribose signalling pathway in duodenum myocytes J. Cell Sci., May 15, 2005; 118(10): 2261 - 2270. [Abstract] [Full Text] [PDF]

				R. Laporte, A. Hui, and I. Laher Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle Pharmacol. Rev., December 1, 2004; 56(4): 439 - 513. [Abstract] [Full Text] [PDF]