Involvement of endogenous nitric oxide in non-adrenergic, non-cholinergic contraction elicited by [Met5]-enkephalin in rat isolated duodenum.
To investigate the possible neuromodulatory role of nitric oxide (NO) in the gastrointestinal tract, an examination was made of the effects of NG-nitro-L-arginine (L-NOARG), an inhibitor of NO synthase, on the intestinal response to [Met5]-enkephalin (ENK) by recording the mechanical activity of the isolated duodenum from rats. [Met5]-enkephalin elicited a biphasic response of the duodenum, i.e. transient relaxation followed by contraction. The relaxation induced by ENK was blocked by naloxone, an opioid receptor antagonist, but not by tetrodotoxin (TTX). The contractile response of the duodenum to ENK was blocked by TTX but not by naloxone. The contractile response was not affected by hyoscine, a muscarinic antagonist, or guanethidine, an adrenergic neuron blocking agent, indicating mediation by non-adrenergic, non-cholinergic (NANC) nerves. The contractile but not the relaxant response to ENK was blocked by L- but not D-NOARG. The contractile response was also inhibited by methylene blue, an inhibitor of both NO synthase and guanylate cyclase, and by indomethacin, a cyclooxygenase inhibitor. Thus, endogenous NO and prostaglandins are involved in the contractile response to ENK. Endogenous NO may modulate the release of excitatory NANC transmitters via a prejunctional mechanism.
Irie
K
K
Department of Pharmacology, Tokyo Women's Medical College, Japan.
Fujii
E
E
Uchida
Y
Y
Muraki
T
T
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D004744:Enkephalin, Methionine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology
D019335:Nitroarginine; D009569:Nitric Oxide; D009270:Naloxone; D013779:Tetrodotoxin; D004744:Enkephalin, Methionine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases