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 mu M) and hydroxocoba lamin (30-100 mu M) concentration-dependently inhibited the relaxation s induced by NO (0.3-30 mu M) but not those by nitroglycerin (GTN, 1 m u M) in the canine ileocolonic junction (ICJ). Hydroxocobalamin reduce d the relaxation to low frequency (2 Hz) stimulation of the non-adrene rgic, non-cholinergic (NANC) nerves, whereas hydroquinone only reduced the NANC nerve-mediated relaxations to electrical stimulation at 16 H z, 0.5 ms. 2 Relaxations to S-nitroso-L-cysteine (CysNO, 1-30 mu M), o r S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-30 mu M) were not inhi bited by hydroquinone (30-100 mu M), hydroxocobalamin (30-100 mu M), p yrogallol (30-100 mu M) or L-cysteine (1-3 mu M). Hydroquinone (100 mu M) only reduced the relaxation to 10 mu M CysNO. Hydroxocobalamin, bu t not hydroquinone, pyrogallol or L-cysteine, potentiated the relaxati ons to the lowest concentration (1 mu M) of S-nitrosoglutathione (GSNO , 1-30 mu M). 3 In the superfusion bioassay, hydroquinone (100 mu M) a nd hydroxocobalamin (1 mu M) concentration-dependently inhibited the b iological activity of authentic NO (1-4 pmol) to the same extent as th at of the transferable nitrergic factor, released from the canine ICJ in response to NANC nerve stimulation (8-16 Hz, 2 ms). Responses to GT N (10 pmol) or adenosine 5'-triphosphate (10 nmol) were not affected. 4 In conclusion, the nitrosothiols CysNO, SNAP and GSNO relax the cani ne ileocolonic junction, but these relaxations, pharmacologically, beh ave differently from the NANC nerve-mediated relaxations. From the bio assay experiments, we conclude that the nitrergic factor, released in response to NANC nerve stimulation of the canine ICJ, behaves pharmaco logically like NO but not like a nitrosothiol. Therefore, we suggest N O, and not CysNO, SNAP or GSNO as the inhibitory NANC neurotransmitter in the ICJ.