Stonustoxin: a highly potent endothelium-dependent vasorelaxant in the rat.
Stonefish venom has been documented to cause marked hypotension and respiratory difficulties in envenomed animals. Stonustoxin, a lethal protein recently isolated from the venom of the stonefish Synanceja horrida produced hypotension and, at concentrations above 20 micrograms/kg, death in anaesthetized rats, with no observable effects on nerve-evoked twitches of the tibialis and diaphragm muscles. Stonustoxin (20-160 ng/ml) induced endothelium-dependent relaxations of rat thoracic aortae precontracted with noradrenaline. Higher concentrations induced relaxations followed by contractions. Methylene blue, haemoglobin and the specific NO-synthase inhibitor L-NG-nitro arginine methyl ester inhibited stonustoxin-induced relaxations, while the cyclooxygenase inhibitor indomethacin was without effect. The results of the present study show that stonustoxin causes marked vasorelaxation of the rat isolated aorta, which appears to be due to the release of endothelium-derived relaxing factor (probably nitric oxide or nitric oxide-yielding substances) from the vascular endothelium, and this may be responsible for the in vivo hypotensive and lethal actions of stonustoxin and of stonefish venom.
Low
K S
KS
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Gwee
M C
MC
Yuen
R
R
Gopalakrishnakone
P
P
Khoo
H E
HE
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005397:Fish Venoms / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009132:Muscles / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D005397:Fish Venoms; D014665:Vasodilator Agents; C073228:stonustoxin; D009569:Nitric Oxide