Linked Life Data

18523136

Source:http://linkedlifedata.com/resource/pubmed/id/18523136

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-8-22
pubmed:abstractText
The P2X(1) receptor-channels activated by extracellular ATP contribute to the neurogenic component of smooth muscle contraction in vascular beds and genitourinary tracts of rodents and humans. In the present study, we investigated the interactions of plasma membrane phosphoinositides with P2X(1) ATP receptors and their physiological consequences. In an isolated rat mesenteric artery preparation, we observed a strong inhibition of P2X(1)-mediated constrictive responses by depletion of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] with the phosphatidylinositol 4-kinase inhibitor wortmannin. Using the Xenopus laevis oocyte expression system, we provided electrophysiological evidence that lowering PI(4,5)P(2) levels with wortmannin significantly decreases P2X(1) current amplitude and recovery. Previously reported modulation of recovery of desensitized P2X(1) currents by phospholipase C-coupled 5-hydroxytryptamine(2A) metabotropic receptors was also found to be wortmannin-sensitive. Treatment with wortmannin alters the kinetics of P2X(1) activation and inactivation without changing its sensitivity to ATP. The functional impact of wortmannin on P2X(1) currents could be reversed by addition of intracellular PI(4,5)P(2), but not phosphatidylinositol 3,4,5-trisphosphate, and direct application of PI(4,5)P(2) to excised inside-out macropatches rescued P2X(1) currents from rundown. We showed that the proximal region of the intracellular C terminus of P2X(1) subunit directly binds to PI(4,5)P(2) and other anionic phospholipids, and we identified the basic residue Lys(364) as a critical determinant for phospholipid binding and sensitivity to wortmannin. Overall, these results indicate that PI(4,5)P(2) plays a key role in the expression of full native and heterologous P2X(1) function by regulating the amplitude, recovery, and kinetics of ionotropic ATP responses through direct receptor-lipid interactions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
785-92
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed-meshheading:18523136-Adenosine Triphosphate, pubmed-meshheading:18523136-Amino Acid Sequence, pubmed-meshheading:18523136-Androstadienes, pubmed-meshheading:18523136-Animals, pubmed-meshheading:18523136-Electrophysiology, pubmed-meshheading:18523136-Ion Channel Gating, pubmed-meshheading:18523136-Kinetics, pubmed-meshheading:18523136-Lysine, pubmed-meshheading:18523136-Mesenteric Arteries, pubmed-meshheading:18523136-Molecular Sequence Data, pubmed-meshheading:18523136-Oocytes, pubmed-meshheading:18523136-Phosphatidylinositol 4,5-Diphosphate, pubmed-meshheading:18523136-Protein Structure, Tertiary, pubmed-meshheading:18523136-Protein Subunits, pubmed-meshheading:18523136-Rats, pubmed-meshheading:18523136-Receptor, Serotonin, 5-HT2A, pubmed-meshheading:18523136-Receptors, Purinergic P2, pubmed-meshheading:18523136-Receptors, Purinergic P2X, pubmed-meshheading:18523136-Recombinant Proteins, pubmed-meshheading:18523136-Vasoconstriction, pubmed-meshheading:18523136-Xenopus
pubmed:year
2008
pubmed:articleTitle
Direct modulation of P2X1 receptor-channels by the lipid phosphatidylinositol 4,5-bisphosphate.
pubmed:affiliation
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural