The role of the L-arginine/nitric oxide pathway for relaxation of the human lower oesophageal sphincter.
Smooth muscle specimens were taken from the oesophagogastric junction (OGJ) in patients operated on for gastrointestinal malignancies not involving the OGJ. The smooth muscle bundles of the inner, circular layer of the OGJ were richly innervated by fine nerve fibres staining positively for NADPH diaphorase. The outer longitudinal layer had a markedly lower number of NADPH-diaphorase positive nerve fibres. When the preparations were suspended in organ baths for recording of isometric tension, they developed active tension. Transmural field stimulation (TMS) induced frequency-dependent relaxations, which were abolished by NG-nitro-L-arginine (L-NNA; 10(-4) M), and were often converted to atropine-sensitive contractions. The effect of L-NNA was concentration-dependent, and the concentration-response curve for L-NNA was shifted to the right by L-arginine pre-incubation. The enantiomer NG-nitro-D-arginine (10(-4) M) also showed inhibitory actions on the responses to TMS, but significantly less than L-NNA. Relaxant responses to vasoactive intestinal polypeptide (VIP), forskolin, and sodium nitroprusside were unaffected by L-NNA pre-incubation. Exposure to a 124 mM K+ solution resulted in a biphasic relaxation of the preparations. This relaxation was not seen in preparations treated with scorpion venom (20 micrograms ml-1) or L-NNA (10(-4) M). Instead, a contractile response to 124 mM K+ solution was found. The results suggest that NANC responses to electrical stimulation of nerves in the human OGJ are mediated by a product generated from L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
Tøttrup
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A
Department of Surgical Gastroenterology L, Aarhus Kommunehospital, Denmark.
Ny
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L
Alm
P
P
Larsson
B
B
Forman
A
A
Andersson
K E
KE
D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004558:Electric Stimulation; D004943:Esophagogastric Junction / Q000187:drug effects / Q000201:enzymology / Q000294:innervation / Q000502:physiology*; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D019335:Nitroarginine; D011188:Potassium / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology
D012604:Scorpion Venoms; D019335:Nitroarginine; D001120:Arginine; D009252:NADPH Dehydrogenase; D011188:Potassium