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First published online August 23, 2004
Journal of Experimental Biology 207, 3411-3417 (2004)
Published by The Company of Biologists 2004
doi: 10.1242/jeb.01134

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Endothelin B receptor Ca²⁺ signaling in shark vascular smooth muscle: participation of inositol trisphosphate and ryanodine receptors

Susan K. Fellner^1,2,* and Laurel A. Parker²

¹ Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
² Mount Desert Island Biological laboratory, Salisbury Cove, ME 04672, USA

^* Author for correspondence (e-mail: sfellner{at}med.unc.edu)

Accepted 10 June 1004

In mammals, endothelin receptors are sub-classified into ET_A receptors (ET_AR), which are purely constrictive in vascular smooth muscle (VSM), and ET_BR, which may produce constriction in VSM or dilatation by stimulating the production of nitric oxide (NO) from endothelial cells. In contrast, previous studies suggested that shark VSM is stimulated exclusively by ET_BR. The Ca²⁺ signaling pathways utilized by shark VSM in response to stimulation by endothelin-1 (ET-1) have not previously been investigated. We measured cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in fura-2-loaded VSM of anterior mesenteric artery of Squalus acanthias and show that the ET_BR agonists IRL 1620 and sarafotoxin S6c (SRX) increase [Ca²⁺]_i in VSM to the same extent as ET-1 and ET_BR appears to be the only ETR subtype in sharks. To investigate the participation of the inositol trisphosphate (IP₃) receptors (IP₃R), we utilized two inhibitors of the mammalian IP₃R, TMB-8 and 2-APB. In Ca²⁺-free Ringer, these agents inhibit the response to ET_BR agonist stimulation by 71%. The ryanodine-sensitive receptor (RyR) may be activated by low concentrations of ryanodine, by abrupt local increases of [Ca²⁺]_i, (calcium-induced calcium release) or by cyclic adeninediphosphate ribose (cADPR). We employed three inhibitors of activation of the RyR, Ruthenium Red, 8-Br cADPR and high concentrations of ryanodine; these agents blocked the [Ca²⁺]_i response to ET_BR agonist stimulation by a mean of 39%. These data show for the first time that in VSM of the shark, ET_BR activation stimulates both IP₃R and RyR, and that cADPR is involved in RyR activation.

Key words: calcium signaling, elasmobranch, cADPR, ryanodine, IP3, dogfish shark, Squalus acanthias

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This article has been cited by other articles:

				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]

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