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Myogenic nitric oxide synthase activity in canine lower oesophageal sphincter: morphological and functional evidence
Author(s) -
Salapatek Anne Marie F.,
Wang YuFang,
Mao YuKang,
Lam Annette,
Daniel Edwin E.
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701701
Subject(s) - nitric oxide synthase , citrulline , medicine , endocrinology , arginine , immunocytochemistry , nitric oxide , endothelial nos , muscle contraction , myogenic contraction , chemistry , biology , nitroarginine , biochemistry , smooth muscle , amino acid , enos
1 Studies on canine lower oesophageal sphincter (LOS) evaluated the existence and function of a myogenic, nitric oxide synthase (NOS) by use of immunocytochemistry for NOS isozymes, NADPH‐d histochemistry, [ 3 H]‐ L ‐arginine to [ 3 H]‐ L ‐citrulline transformation. In addition, functional studies in the muscle bath were performed. 2 Smooth muscle bundles or freshly isolated smooth muscle cells of LOS were NADPH‐d reactive but did not recognize some antibodies against neural, endothelial or inducible NOS. NADPH‐d reactivity and immunoreactivity to a neural NOS antibody were colocalized in LOS enteric nerves. Muscle plasma membrane‐enriched fractions from fresh and cultured LOS cells converted [ 3 H]‐ L ‐arginine to [ 3 H]‐ L ‐citrulline; activity was mostly Ca 2+ /calmodulin‐dependent. 3 N‐Nitro‐ L ‐arginine ( L ‐NOARG) persistently increased tone (blocked by L ‐arginine) in muscle strips despite blockade of nerve function. Nifedipine prevented or abolished L ‐NOARG‐induced, but not carbachol‐induced, contraction showing that tone increase by L ‐NOARG required functional L ‐Ca channels. 4 Membrane‐bound, myogenic NOS in canine LOS may release NO continuously when Ca 2+ entry through L ‐Ca channels occurs under physiological conditions and thereby modulate tone in LOS.British Journal of Pharmacology (1998) 123 , 1055–1064; doi: 10.1038/sj.bjp.0701701