Activation of noradrenergic and nitrergic mechanisms in the rat anococcygeus muscle by nicotine.
1. Nicotine (10 mumol/L) produced rapidly developing but transient contractions of anococcygeus muscle isolated from rats. The magnitude of the response varied considerably between preparations. Tachyphylaxis occurred, such that no response was elicited by the same or a larger concentration in the continued presence of 10 mumol/L nicotine. 2. Contractions produced by nicotine were not affected by atropine, but were abolished by Hexamethonium and the alpha-adrenoceptor antagonists prazosin and phentolamine. Contractions were absent in the anococcygeus muscles of rats pretreated with reserpine. 3. The alpha 2-adrenoceptor agonist UK14304, or guanethidine, raised the tone of the anococcygeus muscle, and converted responses to field stimulation and nicotine to relaxations. Nicotine-induced relaxations were more pronounced in the presence of UK14304 than guanethidine. 4. Relaxations produced by nicotine (1-18 mumol/L) were transient, and tachyphylaxis occurred. When precautions were taken to avoid tachyphylaxis, concentration-response curves could be constructed. The relaxations elicited by nicotine were abolished or greatly reduced by hexamethonium, tetrodotoxin or omega-conotoxin GVIA. 5. The nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (90 mumol/L) enhanced contractile responses to field stimulation and nicotine, and markedly reduced relaxations elicited by field stimulation and nicotine in the presence of UK14304. These relaxations were restored by L-arginine (270 mumol/L). 6. The results suggest that nicotine acts on nicotinic receptors of noradrenergic and nitrergic nerve terminals in the rat anococcygeus muscle, resulting in the release of noradrenaline and nitric oxide respectively.
Rand
M J
MJ
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Li
C G
CG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010276:Parasympatholytics; D010456:Peptides, Cyclic; D009569:Nitric Oxide; D013779:Tetrodotoxin; D009538:Nicotine; D012110:Reserpine; D020866:omega-Conotoxin GVIA; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine