L-arginine-nitric oxide pathway involvement in the nerve-evoked relaxant responses of the 5-HT precontracted chick isolated upper oesophagus.
1. The effects of tetrodotoxin (TTx) and the selective nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on relaxant responses of the 5-HT precontracted chick isolated upper oesophagus to electrical field stimulation (EFS: 25-30V, 5 Hz for 10 s, 1 ms pulse width every 100 s) were investigated; the oesophagus was mounted under 1 g tension in Krebs solution containing 1 microM atropine. Appropriate tissue sections (30 microM thickness) of the chick oesophagus were also processed for NADPH-diaphorase histochemistry. 2. TTx (2 microM) and L-NAME (100-200 microM) inhibited the relaxant responses of the 5-HT precontracted chick oesophagus to EFS in a concentration-dependent manner; L-arginine (0.5-1 mM), but not D-arginine (0.5-1 mM), reversed the inhibition by L-NAME. In the absence of atropine and muscle tone, EFS produced contractile responses of the chick oesophagus that were completely abolished by 1 microM atropine, which also blocked the contractile response to acetylcholine (50 microM). 3. Under light microscopy, NADPH-diaphorase histochemistry confirmed the presence of nitric oxide synthase (NOS)-containing neurones and nerve fibres in the chick oesophagus. 4. The relaxant responses of the 5-HT precontracted chick isolated upper oesophagus to EFS are, therefore, mediated via the stimulation of non-adrenergic non-cholinergic nerves. These are likely to correspond to the histochemically identified NOS-containing neurones involved, presumably, in the synthesis and release of nitric oxide as the relaxant (inhibitory) neurotransmitter in this avian smooth muscle.
Gwee
M C
MC
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Gopalakrishnakone
P
P
Cheah
L S
LS
Bowman
W C
WC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D002645:Chickens; D004558:Electric Stimulation; D004947:Esophagus / Q000187:drug effects; D006651:Histocytochemistry; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D009569:Nitric Oxide; D012701:Serotonin; D013779:Tetrodotoxin; D001120:Arginine; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester