Article date: July 1999
By: C W R Shuttleworth, K M Sweeney, K M Sanders, in Volume 127, Issue 6, pages 1495-1501
Nitric oxide synthase‐containing nerve fibres are abundant within taenia of the guinea‐pig caecum, but there is little previous evidence supporting a direct role for nitric oxide (NO) in responses to enteric inhibitory nerve stimulation. In this study we have attempted to identify an NO‐dependent component of inhibitory transmission in isolated taenia coli.
Isometric tension was recorded in the presence of atropine and guanethidine (both 1 μM). Tone was raised with histamine (1 μM), and intrinsic inhibitory neurons stimulated using either a nicotinic agonist (1,1‐dimethyl‐4‐phenylpiperazinium iodide; DMPP) or electrical field stimulation (EFS).
DMPP (1–100 μM) produced concentration‐dependent biphasic relaxations, comprising an initial peak relaxation followed by a sustained relaxation. Responses to DMPP were antagonized by tetrodotoxin (1 μM) or apamin (0.3 μM) and abolished by hexamethonium (300 μM). L‐nitro‐arginine (L‐NOARG; 100 μM) and oxyhaemoglobin (2%) both significantly reduced sustained relaxations produced by DMPP.
EFS (5 Hz, 30 s) also produced biphasic relaxations. Both L‐NOARG and an inhibitor of soluble guanylate cyclase (ODQ, 1–10 μM) reduced the sustained component of EFS responses.
Two NO donors, sodium nitroprusside (SNP) and diethylenetriamine‐nitric oxide adduct (DENO), produced concentration‐dependent relaxations. Responses to SNP and DENO were antagonized by ODQ (1 μM) and by apamin (0.3 μM).
These results suggest that NO contributes directly to a component of inhibitory transmission in guinea‐pig taenia coli. The actions of NO appear to be mediated via cyclic GMP synthesis, and may involve activation of small conductance calcium activated K+ channels. A role for NO is most evident during sustained relaxations evoked by longer stimulus trains or chemical stimulation of intrinsic neurons.
Nitric oxide synthase‐containing nerve fibres are abundant within taenia of the guinea‐pig caecum, but there is little previous evidence supporting a direct role for nitric oxide (NO) in responses to enteric inhibitory nerve stimulation. In this study we have attempted to identify an NO‐dependent component of inhibitory transmission in isolated taenia coli.
Isometric tension was recorded in the presence of atropine and guanethidine (both 1 μM). Tone was raised with histamine (1 μM), and intrinsic inhibitory neurons stimulated using either a nicotinic agonist (1,1‐dimethyl‐4‐phenylpiperazinium iodide; DMPP) or electrical field stimulation (EFS).
DMPP (1–100 μM) produced concentration‐dependent biphasic relaxations, comprising an initial peak relaxation followed by a sustained relaxation. Responses to DMPP were antagonized by tetrodotoxin (1 μM) or apamin (0.3 μM) and abolished by hexamethonium (300 μM). L‐nitro‐arginine (L‐NOARG; 100 μM) and oxyhaemoglobin (2%) both significantly reduced sustained relaxations produced by DMPP.
EFS (5 Hz, 30 s) also produced biphasic relaxations. Both L‐NOARG and an inhibitor of soluble guanylate cyclase (ODQ, 1–10 μM) reduced the sustained component of EFS responses.
Two NO donors, sodium nitroprusside (SNP) and diethylenetriamine‐nitric oxide adduct (DENO), produced concentration‐dependent relaxations. Responses to SNP and DENO were antagonized by ODQ (1 μM) and by apamin (0.3 μM).
These results suggest that NO contributes directly to a component of inhibitory transmission in guinea‐pig taenia coli. The actions of NO appear to be mediated via cyclic GMP synthesis, and may involve activation of small conductance calcium activated K+ channels. A role for NO is most evident during sustained relaxations evoked by longer stimulus trains or chemical stimulation of intrinsic neurons.
British Journal of Pharmacology (1999) 127, 1495–1501; doi:10.1038/sj.bjp.0702674
DOI: 10.1038/sj.bjp.0702674
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