Characterization of the mechanism underlying stonustoxin-mediated relaxant response in the rat aorta in vitro

Biochemical Pharmacology
Julia Mei Li SungHoon Eng Khoo

Abstract

Stonustoxin (SNTX) is a lethal factor isolated from the venom of the stonefish Synanceja horrida. Although SNTX exhibits a multitude of biological activities, the primary cause of death upon administration of the toxin is attributed to marked hypotension. We investigated the possible mechanisms underlying the vascular hyporeactivity of this novel toxin. Cumulative doses of SNTX (5-320 ng/mL) induced concentration-dependent relaxation in phenylephrine (PE)--precontracted rat aortic rings with intact endothelium. Endothelium removal abolished the relaxation induced by SNTX. Tetraethylammonium (TEA), an inhibitor of K(+) channels, partially inhibited SNTX-induced relaxation. Similarly, SNTX-induced relaxation was partially attenuated by the SP receptor antagonist (NATB), whereas the inducible iNOS inhibitor, AMT-HCl, completely abolished the relaxation caused by SNTX. From the results obtained, it can be postulated that a component of SNTX-mediated vasorelaxation is via binding of either SNTX or SP to the SP receptors that are located on the endothelial cells. Occupation of these SP receptors causes subsequent production of NO and activation of K(+) channels, thus leading to vasorelaxation of the rat aortic rings.

References

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Citations

Aug 8, 2002·Clinical and Experimental Pharmacology & Physiology·Hoon Eng Khoo
Jul 31, 2009·Annual Review of Genomics and Human Genetics·Bryan G FryRicardo C Rodríguez de la Vega
Sep 30, 2008·Pakistan Journal of Biological Sciences : PJBS·Mohammad Kazem Gharib NaseriAkram Ahangarpour
Jun 21, 2014·Toxicon : Official Journal of the International Society on Toxinology·Po-Shun Chuang, Jen-Chieh Shiao
Dec 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Andrew M EllisdonSheena McGowan
May 8, 2016·Toxicon : Official Journal of the International Society on Toxinology·Helena L GomesSuely G Figueiredo
May 25, 2010·Toxicon : Official Journal of the International Society on Toxinology·F AndrichS G Figueiredo
Feb 1, 2017·British Journal of Pharmacology·Chi Ming WongArthur Chi-Kong Chung
Jan 26, 2005·The Journal of Biological Chemistry·Yuh Fen PungR Manjunatha Kini

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