Evidence that nitric oxide acts as an inhibitory neurotransmitter supplying taenia from the guinea-pig caecum

1 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. 2 Isometric tension was recorded in the presence of atropine and guanethidine (both 1 mu M). Tone was raised with histamine (1 mu M), and intrinsic inhibitory neurons stimulated using either a nicotinic agonist (1,1-dimethyl-4-phenylpiperazinium iodide; DMPP) or electrical held stimulation (EFS). 3 DMPP (1-100 mu M) produced concentration-dependent biphasic relaxations, comprising an initial peak relaxation followed by a sustained relaxation. Responses to DMPP were antagonized by tetrodotoxin (1 mu M) or apamin (0.3 mu M) and abolished by hexamethonium (300 mu M). L-nitro-arginine (L-NOARG; 100 mu M) and oxyhaemoglobin (2%) both significantly reduced sustained relaxations produced by DMPP. 4 EFS (5 Hz, 30s) also produced biphasic relaxations. Both L-NOARG and an inhibitor of soluble guanylate cyclase (ODQ, 1-10 mu M) reduced the sustained component of EFS responses. 5 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 (l mu M) and by apamin (0.3 mu M). 6 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.