|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online March 14, 2005
Journal of Experimental Biology 208, 1045-1052 (2005)
Published by The Company of Biologists 2005
doi: 10.1242/jeb.01506
Endothelin-1, superoxide and adeninediphosphate ribose cyclase in shark vascular smooth muscle
1 Mount Desert Island Biological Laboratory, Salisbury Maine 04672
USA
2 Department of Cell and Molecular Physiology, University of North Carolina
at Chapel Hill, Chapel Hill, NC 27599-7545, USA
* Author for correspondence (e-mail: sfellner{at}med.unc.edu)
Accepted 24 January 2005
In vascular smooth muscle (VSM) of Squalus acanthias, endothelin-1 (ET-1) signals via the ETB receptor. In both shark and mammalian VSM, ET-1 induces a rise in cytosolic Ca2+ concentration ([Ca2+]i) via activation of the inositol trisphosphate (IP3) receptor (IP3R) and subsequent release of Ca2+ from the sarcoplasmic reticulum (SR). IP3R-mediated release of SR Ca2+ causes calcium-induced calcium release (CICR) via the ryanodine receptor (RyR), which can be sensitized by cyclic adeninediphosphate ribose (cADPR). cADPR is synthesized from NAD+ by a membrane-bound bifunctional enzyme, ADPR cyclase. We have previously shown that the antagonists of the RyR, Ruthenium Red, high concentrations of ryanodine and 8-Br cADPR, diminish the [Ca2+]i response to ET-1 in shark VSM. To investigate how ET-1 might influence the activity of the ADPR cyclase, we employed inhibitors of the cyclase. To explore the possibility that ET-1-induced production of superoxide (O2.-) might activate the cyclase, we used an inhibitor of NAD(P)H oxidase (NOX), DPI and a scavenger of O2.-, TEMPOL. Anterior mesenteric artery VSM was loaded with fura-2AM to measure [Ca2+]i. In Ca2+-free shark Ringers, ET-1 increased [Ca2+]i by 104±8 nmol l-1. The VSM ADPR cyclase inhibitors, nicotinamide and Zn2+, diminished the response by 62% and 72%, respectively. Both DPI and TEMPOL reduced the response by 63%. The combination of the IP3R antagonists, 2-APB or TMB-8, with DPI or TEMPOL further reduced the response by 83%. We show for the first time that in shark VSM, inhibition of the ADPR cyclase reduces the [Ca2+]i response to ET-1 and that superoxide may be involved in the activation of the cyclase.
Key words: NAD(P)H oxidase, nicotinamide, CICR, ryanodine, calcium, shark, Squalus acanthias
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Malavasi, S. Deaglio, A. Funaro, E. Ferrero, A. L. Horenstein, E. Ortolan, T. Vaisitti, and S. Aydin Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology Physiol Rev, July 1, 2008; 88(3): 841 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Thai, S. K. Fellner, and W. J. Arendshorst ADP-ribosyl cyclase and ryanodine receptor activity contribute to basal renal vasomotor tone and agonist-induced renal vasoconstriction in vivo Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1107 - F1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Fellner and W. Arendshorst Endothelin-A and -B receptors, superoxide, and Ca2+ signaling in afferent arterioles Am J Physiol Renal Physiol, January 1, 2007; 292(1): F175 - F184. [Abstract] [Full Text] [PDF]
|
|
