Linked Life Data

9349636

Source:http://linkedlifedata.com/resource/pubmed/id/9349636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-1-21
pubmed:abstractText
The inhibitory potency of different classes of nitric oxide synthase (NOS) inhibitors (amino acid-based substances, guanidines, isothioureas, imidazoles and indazoles) versus peripheral neuronal NOS in the pig gastric fundus was investigated by studying their influence on electrically induced relaxations in non-adrenergic noncholinergic conditions. Circular muscle strips were mounted for isotonic registration in the presence of atropine and guanethidine, and tone was raised with 5-hydroxytryptamine. Electrical field stimulation (40 V, 0.1 ms, 4 Hz, 10 s) induced short-lasting relaxations. The inhibitory effect of 1-phenylimidazole could not be evaluated because it nearly abolished the 5-hydroxytryptamine-induced tone of the tissues. 7-Nitroindazole, imidazole, 2-iminobiotin and aminoguanidine did not inhibit the electrically induced relaxations, while the other 9 substances tested were able to do so. The influence of the incubation period was tested by studying the inhibitory effect after incubation for 10 up to 60 min. For N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-nitro-L-arginine (L-NNA), L-N5-(1-iminoethyl)-ornithine (L-NIO), L-N6-(1-iminoethyl)-lysine (L-NIL), S-methyl-L-thiocitrulline and S-isopropyl isothiourea there was a moderate increase in the inhibitory effect up to 30 min of incubation so that they were incubated for 30 min to study their inhibitory potency. For L-thiocitrulline, S-methyl isothiourea and S-ethyl isothiourea, an incubation period of 60 min was used. The 9 substances concentration-dependently inhibited the electrically induced relaxations with a maximal inhibitory effect of approximately 80% except for S-methyl isothiourea (Emax of 53%). The overall order of potency was: S-isopropyl isothiourea > S-ethyl isothiourea > or = S-methylL-thiocitrulline > or = L-NNA > L-NIO > L-NAME > S-methyl isothiourea > L-thiocitrulline > L-NIL. While the potency for S-isopropyl isothiourea (EC50: 3.1 x 10(-5) M, n = 6) to S-methyl isothiourea (EC50: 11.5 x 10(-5) M, n = 5) was in the same range, the potency of L-thiocitrulline and L-NIL was clearly lower. This study showed several compounds to be potent inhibitors of peripheral neuronal NOS in the pig gastric fundus while some compounds, that were reported to inhibit brain neuronal NOS were not effective. The EC50 values found for the effective substrates in this functional study may be a guideline for the concentrations required to evaluate the role of NO in NANC neurotransmission in gastrointestinal smooth muscle preparations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-iminobiotin, http://linkedlifedata.com/resource/pubmed/chemical/Biotin, http://linkedlifedata.com/resource/pubmed/chemical/Citrulline, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Isothiuronium, http://linkedlifedata.com/resource/pubmed/chemical/Lysine, http://linkedlifedata.com/resource/pubmed/chemical/N(6)-(1-iminoethyl)lysine, http://linkedlifedata.com/resource/pubmed/chemical/N(G)-iminoethylornithine, http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Nitroarginine, http://linkedlifedata.com/resource/pubmed/chemical/Ornithine, http://linkedlifedata.com/resource/pubmed/chemical/S-methylisothiopseudouronium, http://linkedlifedata.com/resource/pubmed/chemical/S-methylthiocitrulline, http://linkedlifedata.com/resource/pubmed/chemical/Thiourea, http://linkedlifedata.com/resource/pubmed/chemical/etiron, http://linkedlifedata.com/resource/pubmed/chemical/thiocitrulline
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
356
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
488-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Influence of different classes of NO synthase inhibitors in the pig gastric fundus.
pubmed:affiliation
Heymans Institute of Pharmacology, Gent, Belgium.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't