|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0010762,
umls-concept:C0025465,
umls-concept:C0032214,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0035028,
umls-concept:C0035820,
umls-concept:C0205263,
umls-concept:C0299477,
umls-concept:C0596235,
umls-concept:C0870883
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2008-5-7
|
|
pubmed:abstractText |
The perivascular sensory nerve (PvN) Ca(2+)-sensing receptor (CaR) is implicated in Ca(2+)-induced relaxation of isolated, phenylephrine (PE)-contracted mesenteric arteries, which involves the vascular endogenous cannabinoid system. We determined the effect of inhibition of diacylglycerol (DAG) lipase (DAGL), phospholipase A(2) (PLA(2)), and cytochrome P-450 (CYP) on Ca(2+)-induced relaxation of PE-contracted rat mesenteric arteries. Our findings indicate that Ca(2+)-induced vasorelaxation is not dependent on the endothelium. The DAGL inhibitor RHC 802675 (1 microM) and the CYP and PLA(2) inhibitors quinacrine (5 microM) (EC(50): RHC 802675 2.8 +/- 0.4 mM vs. control 1.4 +/- 0.3 mM; quinacrine 4.8 +/- 0.4 mM vs. control 2.0 +/- 0.3 mM; n = 5) and arachidonyltrifluoromethyl ketone (AACOCF(3), 1 microM) reduced Ca(2+)-induced relaxation of mesenteric arteries. Synthetic 2-arachidonoylglycerol (2-AG) and glycerated epoxyeicosatrienoic acids (GEETs) induced concentration-dependent relaxation of isolated arteries. 2-AG relaxations were blocked by iberiotoxin (IBTX) (EC(50): control 0.96 +/- 0.14 nM, IBTX 1.3 +/- 0.5 microM) and miconazole (48 +/- 3%), and 11,12-GEET responses were blocked by IBTX (EC(50): control 55 +/- 9 nM, IBTX 690 +/- 96 nM) and SR-141716A. The data suggest that activation of the CaR in the PvN network by Ca(2+) leads to synthesis and/or release of metabolites of the CYP epoxygenase pathway and metabolism of DAG to 2-AG and subsequently to GEETs. The findings indicate a role for 2-AG and its metabolites in Ca(2+)-induced relaxation of resistance arteries; therefore this receptor may be a potential target for the development of new vasodilator compounds for antihypertensive therapy.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-arachidonylglycerol,
http://linkedlifedata.com/resource/pubmed/chemical/8,11,14-Eicosatrienoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoprotein Lipase,
http://linkedlifedata.com/resource/pubmed/chemical/Miconazole,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels...,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Quinacrine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cannabinoid, CB1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcium-Sensing,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/arachidonyltrifluoromethane,
http://linkedlifedata.com/resource/pubmed/chemical/iberiotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/rimonabant
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
0363-6135
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
294
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
H2363-70
|
|
pubmed:meshHeading |
pubmed-meshheading:18375719-8,11,14-Eicosatrienoic Acid,
pubmed-meshheading:18375719-Acetylcholine,
pubmed-meshheading:18375719-Animals,
pubmed-meshheading:18375719-Arachidonic Acids,
pubmed-meshheading:18375719-Calcium,
pubmed-meshheading:18375719-Cytochrome P-450 Enzyme System,
pubmed-meshheading:18375719-Dose-Response Relationship, Drug,
pubmed-meshheading:18375719-Enzyme Inhibitors,
pubmed-meshheading:18375719-Glycerides,
pubmed-meshheading:18375719-Lipoprotein Lipase,
pubmed-meshheading:18375719-Male,
pubmed-meshheading:18375719-Mesenteric Arteries,
pubmed-meshheading:18375719-Miconazole,
pubmed-meshheading:18375719-Peptides,
pubmed-meshheading:18375719-Phenylephrine,
pubmed-meshheading:18375719-Phospholipases A2,
pubmed-meshheading:18375719-Piperidines,
pubmed-meshheading:18375719-Potassium Channel Blockers,
pubmed-meshheading:18375719-Potassium Channels, Calcium-Activated,
pubmed-meshheading:18375719-Pyrazoles,
pubmed-meshheading:18375719-Quinacrine,
pubmed-meshheading:18375719-Rats,
pubmed-meshheading:18375719-Rats, Wistar,
pubmed-meshheading:18375719-Receptor, Cannabinoid, CB1,
pubmed-meshheading:18375719-Receptors, Calcium-Sensing,
pubmed-meshheading:18375719-Signal Transduction,
pubmed-meshheading:18375719-Vasoconstrictor Agents,
pubmed-meshheading:18375719-Vasodilation,
pubmed-meshheading:18375719-Vasodilator Agents
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Cytochrome P-450 metabolites of 2-arachidonoylglycerol play a role in Ca2+-induced relaxation of rat mesenteric arteries.
|
|
pubmed:affiliation |
Cardiovascular Disease Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC 27707, USA. eawumey@nccu.edu
|
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|
