Endogenous vasoactive intestinal peptide and nitric oxide modulate cholinergic neurotransmission in guinea-pig trachea. 1993

M G Belvisi, and M Miura, and D Stretton, and P J Barnes
Department of Thoracic Medicine, National Heart and Lung Institute, Chelsea, London, UK.

Guinea-pig tracheal smooth muscle possesses an inhibitory non-adrenergic, non-cholinergic (i-NANC) innervation and the neurotransmitters involved in this response may be vasoactive intestinal peptide (VIP) and nitric oxide (NO). Since i-NANC mechanisms may co-exist with cholinergic nerves we have investigated whether endogenous VIP and NO modulate cholinergic neurotransmission. alpha-Chymotrypsin enhanced the cholinergic contractile responses to electrical field stimulation (EFS at 4 Hz by 38.6 +/- 4.8% (P < 0.05, n = 6) but did not produce a shift in the concentration-response curve to acetylcholine (ACh). L-NG-Nitro-arginine methyl ester (L-NAME) and L-NG-monomethyl arginine (L-NMMA) produced a concentration-dependent enhancement of cholinergic responses to EFS (4 Hz) (at 100 microM, 40.9 +/- 6.6 and 30.2 +/- 5.8%, P < 0.01) with no effect on response curves to ACh. This enhancement was reversed by L-arginine but not D-arginine (1 mM). D-NAME and D-NMMA and L-arginine had no effect on cholinergic neurotransmission. alpha-Chymotrypsin and L-NAME had no effect on excitatory NANC (e-NANC) neural responses in guinea-pig bronchi. These results suggest that endogenous NO and VIP may modulate cholinergic neurotransmission by either functional antagonism at the level of the airway smooth muscle or via a pre-junctional inhibition of ACh release from cholinergic nerve terminals or by both mechanisms.

UI MeSH Term Description Entries
D008297 Male Males
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
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
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D002918 Chymotrypsin A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side. Alpha-Chymotrypsin Choay,Alphacutanée,Avazyme
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000594 Amino Acid Oxidoreductases A class of enzymes that catalyze oxidation-reduction reactions of amino acids. Acid Oxidoreductases, Amino,Oxidoreductases, Amino Acid

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