Source:http://linkedlifedata.com/resource/pubmed/id/16919264
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-3
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| pubmed:dateCreated |
2006-9-11
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| pubmed:abstractText |
Nitric oxide synthase (NOS) converts L-arginine into nitric oxide (NO) and L-citrulline. In NO-producing cells, L-citrulline can be recycled to L-arginine in a two-step reaction involving argininosuccinate synthase (ASS) and -lyase (ASL). In guinea pig trachea, L-arginine is a limiting factor in neuronal nNOS-mediated airway smooth muscle relaxation upon inhibitory nonadrenergic noncholinergic (iNANC) nerve stimulation. Moreover, in a guinea pig model of asthma iNANC nerve-induced NO production and airway smooth muscle relaxation are impaired after the allergen-induced early asthmatic reaction, due to limitation of L-arginine. Using guinea pig tracheal preparations, we now investigated whether (i) the L-citrulline/L-arginine cycle is active in airway iNANC nerves and (ii) the NO deficiency after the early asthmatic reaction involves impaired L-citrulline recycling. Electrical field stimulation-induced relaxation was measured in tracheal open-rings precontracted with histamine. L-citrulline as well as the ASL inhibitor succinate did not affect electrical field stimulation-induced relaxation under basal conditions. However, reduced relaxation induced by a submaximal concentration of the NOS inhibitor N(omega)-nitro-L-arginine was restored by L-citrulline, which was prevented by the additional presence of succinate or the ASS inhibitor alpha-methyl-D,L-aspartate. Remarkably, the impaired iNANC relaxation after the early asthmatic reaction was restored by L-citrulline. In conclusion, the L-citrulline/L-arginine cycle is operative in guinea pig iNANC nerves in the airways and may be effective under conditions of low L-arginine utilization by nNOS (caused by NOS inhibitors), and during reduced L-arginine availability after allergen challenge. Enzymatic dysfunction in the L-citrulline/L-arginine cycle appears not to be involved in the L-arginine limitation and reduced iNANC activity after the early asthmatic reaction.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-methylaspartic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Allergens,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Argininosuccinate Lyase,
http://linkedlifedata.com/resource/pubmed/chemical/Argininosuccinate Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Citrulline,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/Succinic Acid
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0014-2999
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
28
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| pubmed:volume |
546
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
171-6
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| pubmed:meshHeading |
pubmed-meshheading:16919264-Allergens,
pubmed-meshheading:16919264-Animals,
pubmed-meshheading:16919264-Arginine,
pubmed-meshheading:16919264-Argininosuccinate Lyase,
pubmed-meshheading:16919264-Argininosuccinate Synthase,
pubmed-meshheading:16919264-Asthma,
pubmed-meshheading:16919264-Citrulline,
pubmed-meshheading:16919264-Disease Models, Animal,
pubmed-meshheading:16919264-Electric Stimulation,
pubmed-meshheading:16919264-Enzyme Inhibitors,
pubmed-meshheading:16919264-Guinea Pigs,
pubmed-meshheading:16919264-Male,
pubmed-meshheading:16919264-Muscle, Smooth,
pubmed-meshheading:16919264-Muscle Relaxation,
pubmed-meshheading:16919264-N-Methylaspartate,
pubmed-meshheading:16919264-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:16919264-Neural Inhibition,
pubmed-meshheading:16919264-Neurons,
pubmed-meshheading:16919264-Nitric Oxide,
pubmed-meshheading:16919264-Nitric Oxide Synthase Type I,
pubmed-meshheading:16919264-Ovalbumin,
pubmed-meshheading:16919264-Specific Pathogen-Free Organisms,
pubmed-meshheading:16919264-Succinic Acid,
pubmed-meshheading:16919264-Trachea
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| pubmed:year |
2006
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| pubmed:articleTitle |
Role of the L-citrulline/L-arginine cycle in iNANC nerve-mediated nitric oxide production and airway smooth muscle relaxation in allergic asthma.
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| pubmed:affiliation |
Department of Molecular Pharmacology, University Centre for Pharmacy, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. h.maarsingh@rug.nl
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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