title: Evidence that nitric oxide acts as an inhibitory neurotransmitter supplying taenia from the guinea-pig caecum.
abstract: 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 microM). Tone was raised with histamine (1 microM), 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 microM) produced concentration-dependent biphasic relaxations, comprising an initial peak relaxation followed by a sustained relaxation. Responses to DMPP were antagonized by tetrodotoxin (1 microM) or apamin (0.3 microM) and abolished by hexamethonium (300 microM). L-nitro-arginine (L-NOARG; 100 microM) 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 microM) 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 microM) and by apamin (0.3 mM). 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.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno 89557, USA. bshuttle@unm.edu
authors.forename: C W
authors.initials: CW
authors.lastname: Shuttleworth
authors.forename: K M
authors.initials: KM
authors.lastname: Sweeney
authors.forename: K M
authors.initials: KM
authors.lastname: Sanders
mesh_terms: D000818:Animals; D002432:Cecum / Q000187:drug effects / Q000502:physiology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000502:physiology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D018722:Nicotinic Agonists; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; D006162:Guanylate Cyclase