Biomaterial Database

Involvement of nitric oxide in the mediation of NANC inhibitory neurotransmission of guinea-pig trachea. 1998

C S Venugopalan, and M J Krautmann, and E P Holmes, and T J Maher

Department of Veterinary Physiology, Pharmacology & Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.

1. The involvement of nitric oxide (NO) in the non-adrenergic non-cholinergic inhibitory (NANC-i) neurotransmission was evaluated in guinea-pigs anaesthetized with chloralose-urethane, using a tracheal pouch preparation. 2. The tracheal pouch, a surgically isolated segment of trachea with intact nerve and blood supply, is an in situ method to demonstrate NANC-i response after complete cholinergic and adrenergic blockade using atropine (5 mg kg(-1)) and propranolol (1 mg kg(-1)), respectively. Cervical vagi and sympathetic trunks were isolated and cut cranially. The distal ends of the vagi were positioned on bipolar electrodes for subsequent stimulation with 5 V pulses for 2 ms duration at 15 Hz for a total of 90 s. The relaxation response was measured as a pressure drop (cm of H2O) in the pouch. Each experimental group was composed of six animals. 3. NANC-i responses to two consecutive nerve stimulations at 25 min apart were reproducible. 4. Pouch relaxation responses to electrical nerve stimulations were determined before and after incubation of the pouch with N(omega)-nitro-L-arginine methyl ester (L-NAME; 10(-5) M), a NO synthase (NOS) inhibitor, for 30 min. L-NAME significantly, but not completely, inhibited the NANC-i response of the pouch, suggesting involvement of NO in the NANC-i neurotransmission. 5. The pouch relaxations to vagal stimulations were inhibited significantly after incubation with oxyHb indicating that NO was released. 6. The amount of methaemoglobin (metHb) formed from oxyhaemoglobin (oxyHb) during vagal stimulation was measured by spectrophotometry. Comparison of the values between the control and after nerve stimulation indicated a trend (P = 0.07) toward greater metHb formation in the pouch perfusate after nerve stimulation. 7. NANC-i responses were not significantly inhibited by incubation of the pouch with either of the guanylate cyclase inhibitors, methylene blue or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). However, a trend toward significance (P < or = 0.07) was observed. 8. This study demonstrated that NO is involved in NANC-i neurotransmission. However, the findings did not conclusively support the contention that NO is the sole neurotransmitter of NANC inhibition. It is possible that NO produced relaxation of guinea-pig trachea through a cGMP-independent mechanism.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008706	Methemoglobin		Ferrihemoglobin
D008751	Methylene Blue	A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.	Methylthionine Chloride,Swiss Blue,Basic Blue 9,Chromosmon,Methylene Blue N,Methylthioninium Chloride,Urolene Blue,Blue 9, Basic,Blue N, Methylene,Blue, Methylene,Blue, Swiss,Blue, Urolene
D009433	Neural Inhibition	The function of opposing or restraining the excitation of neurons or their target excitable cells.	Inhibition, Neural
D009435	Synaptic Transmission	The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.	Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010069	Oxadiazoles	Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms.	Oxadiazole
D011810	Quinoxalines		Quinoxaline
D011941	Receptors, Adrenergic	Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.	Adrenergic Receptors,Adrenoceptor,Adrenoceptors,Norepinephrine Receptor,Receptors, Epinephrine,Receptors, Norepinephrine,Adrenergic Receptor,Epinephrine Receptors,Norepinephrine Receptors,Receptor, Adrenergic,Receptor, Norepinephrine
D011950	Receptors, Cholinergic	Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.	ACh Receptor,Acetylcholine Receptor,Acetylcholine Receptors,Cholinergic Receptor,Cholinergic Receptors,Cholinoceptive Sites,Cholinoceptor,Cholinoceptors,Receptors, Acetylcholine,ACh Receptors,Receptors, ACh,Receptor, ACh,Receptor, Acetylcholine,Receptor, Cholinergic,Sites, Cholinoceptive