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An investigation of some S‐nitrosothiols, and of hydroxy‐arginine, on the mouse anococcygeus
Author(s) -
Gibson A.,
Babbedge R.,
Brave S.R.,
Hart S.L.,
Hobbs A.J.,
Tucker J.F.,
Wallace P.,
Moore P.K.
Publication year - 1992
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.1476-5381.1992.tb14512.x
Subject(s) - chemistry , nitric oxide , carbachol , hydroxylamine , nitric oxide synthase , penicillamine , cysteine , s nitrosoglutathione , cholinergic , biochemistry , arginine , nitrite , snap , stereochemistry , endocrinology , glutathione , enzyme , biology , nitrate , receptor , computer graphics (images) , organic chemistry , amino acid , computer science
1 The effect of five S‐nitrosothiols, and of the stereoisomers of N G ‐hydroxy‐arginine (HOARG), were investigated on the mouse anococcygeus. 2 All five S‐nitrosothiols produced concentration‐related (0.1–100 μ m ) relaxations of carbachol (50 μ m )‐induced tone; the order of potency was S‐nitroso‐ l ‐cysteine (CYSNO) > S‐nitroso‐N‐acetyl‐ d , l ‐penicillamine (SNAP) > S‐nitrosoglutathione (GSNO) > S‐nitrosocoenzyme A (CoASNO) > S‐nitroso‐N‐acetyl‐ l ‐cysteine (NACNO). The relaxations were unaffected by the nitric oxide synthase (NOS) inhibitor, l ‐N G ‐nitro‐arginine (10 μ m ) ( l ‐NOARG). 3 Cold‐storage of the tissue for 72 h resulted in loss of sympathetic and non‐adrenergic, non‐cholinergic (NANC) nerve function. NOS activity in the tissue was reduced by 97%. Despite this, relaxations induced by the S‐nitrosothiols were unaffected. 4 Haemoglobin (50 μ m ) attenuated relaxations induced by NO and the S‐nitrosothiols, although responses to 3‐isobutyl‐1‐methyl‐xanthine were unaffected. N‐methyl‐hydroxylamine (2 M m ) which has been shown previously to produce selective inhibition of NANC and nitrovasodilator responses in this tissue, also reduced responses to all S‐nitrosothiols. 5 Hydroquinone (100 μ m ) greatly reduced relaxations to CYSNO (by 88%) but had no effect on those to SNAP, GSNO, CoASNO or NACNO. Since hydroquinone does not reduce responses to NANC stimulation, CYSNO is unlikely to be the NANC transmitter. 6 l ‐HOARG by itself (up to 100 μ m ) had no significant effect on carbachol‐induced tone or on NANC (10 Hz; 10 s train every 100 s) relaxations. However, it produced reversal of the inhibitory effects of l ‐NOARG (10 μ m ), being only slightly less potent than l ‐arginine. d ‐HOARG was without effect. l ‐HOARG had no effect on relaxations induced by 1.5 μ m NO. 7 The results show that S‐nitrosothiols are potent relaxants of the mouse anococcygeus; they act directly on the smooth muscle with a mechanism similar to NO and other nitrovasodilators. In addition, the results are consistent with l ‐HOARG being an intermediate in the biosynthesis of NO from l ‐arginine, although there is no evidence for it acting to stabilize NO extracellularly.