Involvement of the L-arginine-nitric oxide synthase pathway in the relaxant responses of the rat isolated anococcygeus muscle to a scorpion (Leiurus quinquestriatus quinquestriatus) venom.
Venom from several species of scorpions can cause generalized depolarization of peripheral nerves with enhancement of neurotransmitter release. The effects of the venom (LQV) from the scorpion Leiurus quinquestriatus quinquestriatus were investigated using the rat isolated carbachol (CCh) precontracted anococcygeus muscle (Acm) mounted in Krebs solution containing phentolamine (5 microM). LQV (0.2 microgram/ml and 1.5 micrograms/ml) markedly relaxed the tone of the CCh precontracted (non-stimulated) Acm by 31.5 +/- 5.1% and 35.5 +/- 4.7%, respectively; the onset was immediate after the high dose, followed by a slow and gradual return of the muscle tone to 88.7 +/- 1.8% of the initial peak tension in 50.2 +/- 4 min. Subsequent doses of LQV produced essentially no appreciable changes in muscle tone, but the addition of L-arginine (250 microM) or, especially sodium nitroprusside (SNP; 1 microM) produced marked and rapid relaxations of the Acm. Similar results were obtained with LQV during electrical field stimulation (EFS) of the precotracted Acm; however, during the gradual return of the muscle tone from the relaxed state induced by LQV, the EFS-induced relaxant (NANC) responses were also progressively inhibited by 84.9 +/- 3.4% and 64.3 +/- 4.5 by LQV 0.2 microgram/ml and 1.5 micrograms/ml, respectively. Tetrodotoxin (TTx; 2 microM) or NG-nitro-L-arginine methylester (L-NAME; 50 microM) markedly inhibited the relaxant responses of the Acm to EFS as well as to LQV but not the responses to SNP: L-arginine (250 microM) partially restored the relaxant (NANC) responses of the Acm to EFS. Thus, the L-arginie-nitric oxide synthase-nitric oxide pathway is involved in mediating the marked relaxant responses of the CCh precontracted Acm to LQO.
Gwee
M C
MC
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore.
Cheah
L S
LS
Gopalakrishnakone
P
P
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D012604:Scorpion Venoms; D014665:Vasodilator Agents; D009599:Nitroprusside; D013779:Tetrodotoxin; D002217:Carbachol; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester