P2Y(1) Receptor Activation Elicits Its Partition out of Membrane Rafts and Its Rapid Internalization from Human Blood Vessels: Implications for Receptor Signaling

Simple item page
dc.contributor.authorNorambuena, Andres
dc.contributor.authorPoblete, M. Ines
dc.contributor.authorDonoso, M. Veronica
dc.contributor.authorEspinoza, C. Sofia
dc.contributor.authorGonzalez, Alfonso
dc.contributor.authorHuidobro Toro, J. Pablo
dc.date.accessioned2024-01-10T13:51:44Z
dc.date.available2024-01-10T13:51:44Z
dc.date.issued2008
dc.description.abstractThe nucleotide P2Y(1) receptor ( P2Y(1) R) is expressed in both the endothelial and vascular smooth muscle cells; however, its plasma membrane microregionalization and internalization in human tissues remain unknown. We report on the role of membrane rafts in P2Y(1) R signaling by using sodium carbonate or OptiPrep sucrose density gradients, Western blot analysis, reduction of tissue cholesterol content, and vasomotor assays of endothelium-denuded human chorionic arteries. In tissue extracts prepared either in sodium carbonate or OptiPrep, approximately 20 to 30% of the total P2Y(1) R mass consistently partitioned into raft fractions and correlated with vasomotor activity. Vessel treatment with methyl beta-cyclodextrin reduced the raft partitioning of the P2Y(1) R and obliterated the P2Y(1) R-mediated contractions but not the vasomotor responses elicited by either serotonin or KCl. Perfusion of chorionic artery segments with 100 nM 2-methylthio ADP or 10 nM [[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl] 2,3dihydroxybicyclo[3.1.0] hex-1-yl]methyl] diphosphoric acid mono ester trisodium salt (MRS 2365), a selective P2Y(1) R agonist, not only displaced within 4 min the P2Y(1) R localization out of membrane rafts but also induced its subsequent internalization. 2'-Deoxy-N-6-methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS 2179), a specific P2Y(1) R antagonist, did not cause a similar displacement but blocked the agonist-induced exit from rafts. Neither adenosine nor uridine triphosphate displaced the P2Y(1) R from the membrane raft, further evidencing the pharmacodynamics of the receptor-ligand interaction. Vascular reactivity assays showed fading of the ligand-induced vasoconstrictions, a finding that correlated with the P2Y(1) R exit from raft domains and internalization. These results demonstrate in intact human vascular smooth muscle the association of the P2Y(1) R to membrane rafts, highlighting the role of this microdomain in P2Y(1) R signaling.
dc.description.funderCentre for Cell Regulation and Pathology
dc.description.funderMIFAB
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1124/mol.108.048496
dc.identifier.eissn1521-0111
dc.identifier.issn0026-895X
dc.identifier.pubmedidMEDLINE:18799799
dc.identifier.urihttps://doi.org/10.1124/mol.108.048496
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79622
dc.identifier.wosidWOS:000261003600018
dc.information.autorucCiencias Biológicas;Donoso M;S/I;100241
dc.information.autorucCiencias Biológicas;Espinoza C;S/I;142389
dc.information.autorucMedicina;González A;S/I;52306
dc.information.autorucCiencias Biológicas;Huidobro-Toro J;S/I;98862
dc.information.autorucCiencias Biológicas;Norambuena A;S/I;94539
dc.issue.numero6
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1677
dc.pagina.inicio1666
dc.publisherAMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
dc.revistaMOLECULAR PHARMACOLOGY
dc.rightsacceso restringido
dc.subjectLIPID RAFTS
dc.subjectHETERO-OLIGOMERIZATION
dc.subjectCARDIOVASCULAR-SYSTEM
dc.subjectNUCLEOTIDE RECEPTORS
dc.subjectEPITHELIAL-CELLS
dc.subjectP2X RECEPTORS
dc.subjectADP RECEPTOR
dc.subjectCAVEOLAE
dc.subjectIDENTIFICATION
dc.subjectMICRODOMAINS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleP2Y(1) Receptor Activation Elicits Its Partition out of Membrane Rafts and Its Rapid Internalization from Human Blood Vessels: Implications for Receptor Signaling
dc.typeartículo
dc.volumen74
sipa.codpersvinculados100241
sipa.codpersvinculados142389
sipa.codpersvinculados52306
sipa.codpersvinculados98862
sipa.codpersvinculados94539
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
P2Y1 receptor activation elicits its partition out of membrane rafts and its rapid internalization from human blood vessels - implications for receptor signaling.pdf
Size:
3.52 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas