Multiple inhibitory mechanisms mediate non-adrenergic non-cholinergic relaxation in the circular muscle of the guinea-pig colon.
The mechanisms responsible for nerve-mediated, non-adrenergic, non-cholinergic (NANC) relaxation in mucosa-free circular muscle strips from the proximal colon of the guinea-pig were investigated. Electrical field stimulation (EFS, 1-20 Hz, trains of 5 s duration, 100 V, 0.25 ms pulse width) in the presence of atropine (1 mumol/l) and guanethidine (3 mumol/l) evoked a triphasic motor response consisting of: (a) a primary relaxation, (b) a rebound contraction and (c) a secondary relaxation. These three responses were abolished by tetrodotoxin (1 mumol/l). B oth apamin (0.01-0.3 mumol/l), a known blocker of low conductance, calcium-activated potassium channels in smooth muscles, and L-nitro-arginine (L-NOARG) (1-100 mumol/l), a known blocker of nitric oxide (NO) synthase, increased the tone of the strips. Maximum effects on tone were observed with 0.1 mumol/l apamin (21 +/- 3% of KCl-induced contraction) and 30 mumol/l L-NOARG (26 +/- 4% of KCl response). The combined administration of 0.1 mumol/l apamin and 30 mumol/l L-NOARG produced an increase in tone (47 +/- 5% of KCl response) that was larger than that produced by either compound alone. Neither apamin (0.1 mumol/l) nor L-NOARG (30 mumol/l) affected the isoprenaline-induced relaxation. Apamin (0.1 mumol/l) depressed, but did not abolish, the primary relaxation to EFS at all frequencies without affecting the secondary relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
Maggi
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CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
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S
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019335:Nitroarginine; D011189:Potassium Chloride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D019335:Nitroarginine; D001030:Apamin; D013779:Tetrodotoxin; D011189:Potassium Chloride; D001120:Arginine; D006145:Guanethidine