Comparison of the pharmacological profile of S-nitrosothiols, nitric oxide and the nitrergic neurotransmitter in the canine ileocolonic junction.
1. In organ bath experiments, hydroquinone (30-100 microM) and hydroxocobalamin (30-100 microM) concentration-dependently inhibited the relaxations induced by NO (0.3-30 microM) but not those by nitroglycerin (GTN, 1 microM) 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 microM), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-30 microM) were not inhibited by hydroquinone (30-100 microM), hydroxocobalamin (30-100 microM), pyrogallol (30-100 microM) or L-cysteine (1-3 microM). Hydroquinone (100 microM) only reduced the relaxation to 10 microM CysNO. Hydroxocobalamin, but not hydroquinone, pyrogallol or L-cysteine, potentiated the relaxations to the lowest concentration (1 microM) of S-nitrosoglutathione (GSNO, 1-30 microM). 3. In the superfusion bioassay, hydroquinone (100 microM) and hydroxocobalamin (1 microM) concentration-dependently inhibited the biological activity of authentic NO (1-4 pmol) 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 NANCnerve 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.
De Man
J G
JG
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), Antwerpen-Wilrijk, Belgium.
Boeckxstaens
G E
GE
De Winter
B Y
BY
Moreels
T G
TG
Misset
M E
ME
Herman
A G
AG
Pelckmans
P A
PA
D000818:Animals; D001681:Biological Assay; D003106:Colon / Q000187:drug effects* / Q000294:innervation; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006873:Hydroquinones / Q000494:pharmacology; D006879:Hydroxocobalamin / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D006873:Hydroquinones; D009603:Nitroso Compounds; D017981:Receptors, Neurotransmitter; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D006879:Hydroxocobalamin; C031927:hydroquinone