Characterization of the mechanism underlying stonustoxin-mediated relaxant response in the rat aorta in vitro.
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.
Sung
Julia Mei Li
JM
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Low
Kerwin Siew Yang
KS
Khoo
Hoon Eng
HE
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005397:Fish Venoms / Q000494:pharmacology*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D013843:Thiazines / Q000494:pharmacology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
C093124:2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine; D004791:Enzyme Inhibitors; D005397:Fish Venoms; D064729:Neurokinin-1 Receptor Antagonists; D026902:Potassium Channel Blockers; D013843:Thiazines; C073228:stonustoxin; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D013373:Substance P; D014364:Tryptophan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat