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Comparison of the pharmacological profile of S‐nitrosothiols, nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction
Author(s) -
Man Joris G.,
Boeckxstaens Guy E.,
Winter Benedicte Y.,
Moreels Tom G.,
Misset Menno E.,
Herman Arnold G.,
Pelckmans Paul A.
Publication year - 1995
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.1476-5381.1995.tb13331.x
Subject(s) - hydroxocobalamin , chemistry , hydroquinone , acetylcholine , nitric oxide , cysteine , stimulation , penicillamine , pharmacology , pyrogallol , molsidomine , biophysics , biochemistry , endocrinology , medicine , organic chemistry , biology , cyanocobalamin , vitamin b12 , enzyme
1 In organ bath experiments, hydroquinone (30–100 μ m ) and hydroxocobalamin (30–100 μ m ) concentration‐dependently inhibited the relaxations induced by NO (0.3–30 μ m ) but not those by nitroglycerin (GTN, 1 μ m ) in the canine ileocolonic junction (ICJ). Hydroxocobalamin reduced the relaxation to low frequency (2 Hz) stimulation of the non‐adrenergic, non‐cholinergic (NANC) nerves, whereas hydroquinone only reduced the NANC nerve‐mediated relaxations to electrical stimulation at 16 Hz, 0.5 ms. 2 Relaxations to S‐nitroso‐ l ‐cysteine (CysNO, 1–30 μ m ), or S‐nitroso‐N‐acetyl‐ d,l ‐penicillamine (SNAP, 1–30 μ m ) were not inhibited by hydroquinone (30–100 μ m ), hydroxocobalamin (30–100 μ m ), pyrogallol (30–100 μ m ) or l ‐cysteine (1–3 μ m ). Hydroquinone (100 μ m ) only reduced the relaxation to 10 μ m CysNO. Hydroxocobalamin, but not hydroquinone, pyrogallol or m ‐cysteine, potentiated the relaxations to the lowest concentration (1 μ m ) of S‐nitrosoglutathione (GSNO, 1–30 μ m ). 3 In the superfusion bioassay, hydroquinone (100 μ m ) and hydroxocobalamin (1 μ m ) concentration‐dependently inhibited the biological activity of authentic NO (1–4pmol) to the same extent as that of the transferable nitrergic factor, released from the canine ICJ in response to NANC nerve stimulation (8–16 Hz, 2 ms). Responses to GTN (10 pmol) or adenosine 5′‐triphosphate (10 nmol) were not affected. 4 In conclusion, the nitrosothiols CysNO, SNAP and GSNO relax the canine ileocolonic junction, but these relaxations, pharmacologically, behave differently from the NANC nerve‐mediated relaxations. From the bioassay experiments, we conclude that the nitrergic factor, released in response to NANC nerve stimulation of the canine ICJ, behaves pharmacologically like NO but not like a nitrosothiol. Therefore, we suggest NO, and not CysNO, SNAP or GSNO as the inhibitory NANC neurotransmitter in the canine ICJ.