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Nitric oxide synthase activity and non‐adrenergic non‐cholinergic relaxation in the rat gastric fundus
Author(s) -
Currò; Diego,
Volpe; Anna Rita,
Preziosi Paolo
Publication year - 1996
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 - 10.1111/j.1476-5381.1996.tb15249.x
Subject(s) - endocrinology , medicine , nitric oxide synthase , guanethidine , chemistry , citrulline , tetrodotoxin , nitric oxide , arginine , stimulation , biochemistry , biology , amino acid
1 In the presence of atropine (1 μ m ) and guanethidine (5 μ m ), electrical field stimulation (EFS, 120 mA, 1 ms, 0.5–16.0 Hz, trains of 2 min) induced frequency‐dependent relaxations of 5‐hydroxytryptamine (3 μ m )‐precontracted longitudinal muscle strips from the rat gastric fundus. 2 L‐Citrulline concentrations were measured in the incubation medium of precontracted strips before and after EFS to investigate nitric‐oxide (NO) synthase activity and its possible relation to non‐adrenergic non‐cholinergic (NANC) relaxation. 3 Basal NO synthase activity was reflected by the finding of prestimulation levels of L‐citrulline of 30 nM. These levels were unaffected by tetrodotoxin (3 μ m ) and N G ‐nitro‐D‐arginine methyl ester (D‐NAME, 100 μ m ), slightly reduced by a calcium‐free medium and halved by N G ‐nitro‐L‐arginine methyl ester (L‐NAME, 100 μ m ). 4 EFS evoked significant, frequency‐dependent increases in bath levels of L‐citrulline at all frequencies tested. The increases evoked by 16‐Hz EFS were abolished by tetrodotoxin (3 μ m ), a calcium‐free medium and L‐NAME (100 μ m ) but not by D‐NAME (100 μ m ). 5 L‐NAME (0.1 μ m − 1.0 mM) produced significant reduction of 4‐Hz EFS‐induced L‐citrulline production (100% inhibition at 10 μ m ), but had less marked effects on basal production (50% reduction at 100 μ m ) and 4‐Hz EFS‐induced NANC relaxation (50% reduction at 1 mM). 6 L‐Arginine (1 mM), but not D‐arginine (1 mM), increased basal L‐citrulline levels and reversed the inhibitory effect of L‐NAME (10 μ m ). 7 These findings represent clear biochemical evidence of both basal and EFS‐stimulated NO synthase activity in the rat gastric fundus.