Adrenergic and nitrergic responses of the rat isolated anococcygeus muscle to a new toxin (makatoxin I) from the venom of the scorpion Buthus martensi Karsch.
1. Makatoxin I (MkTx I) is a new toxin purified from the venom of the scorpion Buthus martensi Karsch. Contractile (excitatory, adrenergic) and relaxant (inhibitory, nitrergic) responses of the rat isolated anococcygeus muscle (Acm) to MkTx I were investigated. 2. MkTx I (0.28 microM) produced a rapid and very marked rise in the tone of the Acm which then gradually wanted to the control baseline. Phentolamine (5 microM), guanethidine (5 microM), tetrodotoxin (2 microM) and reserpine pretreatment in vivo (5 mg kg-1 s.c. at 24 hr and 5 mg kg-1 i.p. at 3 h) completely blocked the contractile responses of the Acm to MkTx I. The responses to noradrenaline (NA) were blocked by phentolamine, but were potentiated by guanethidine. 3. MkTx I (0.28 microM) also marked and rapidly relaxed the tone of the carbachol (CCh; 3 microM), precontracted Acm. The addition of sodium nitroprusside (SNP; 1 microM) also produced a marked and rapid relaxation of the Acm. TTx (2 microM) or NG-nitro-L-arginine methylester (L-NAME, 50 microM) markedly inhibited the relaxant responses of the Acm to field stimulation (FS) as well as to MkTx I, but not the responses to SNP. 4. Therefore, the contractile responses of the rat anococcygeus muscle to MkTx I can be attributed to the release of transmitter NA on postjunctional alpha-adrenoceptors, whereas the relaxant responses of the Acm to MkTx I involve the release of nitric oxide as the neurotransmitter which, presumably, results in the activation of the enzyme guanylate cyclase leading to relaxation of the muscle.
Gong
J P
JP
Department of Anatomy, Faculty of Medicine, National University of Singapore, Singapore.
Gwee
M C
MC
Gopalakrishnakone
P
P
Kini
R M
RM
Chung
M C
MC
D000595:Amino Acid Sequence; D000818:Animals; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009125:Muscle Relaxants, Central; D012604:Scorpion Venoms; C105338:makatoxin I; D009569:Nitric Oxide; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester