P2Y(1) Receptor Activation Elicits Its Partition out of Membrane Rafts and Its Rapid Internalization from Human Blood Vessels: Implications for Receptor Signaling
dc.contributor.author | Norambuena, Andres | |
dc.contributor.author | Poblete, M. Ines | |
dc.contributor.author | Donoso, M. Veronica | |
dc.contributor.author | Espinoza, C. Sofia | |
dc.contributor.author | Gonzalez, Alfonso | |
dc.contributor.author | Huidobro Toro, J. Pablo | |
dc.date.accessioned | 2024-01-10T13:51:44Z | |
dc.date.available | 2024-01-10T13:51:44Z | |
dc.date.issued | 2008 | |
dc.description.abstract | The 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.funder | Centre for Cell Regulation and Pathology | |
dc.description.funder | MIFAB | |
dc.fechaingreso.objetodigital | 2024-05-14 | |
dc.format.extent | 12 páginas | |
dc.fuente.origen | WOS | |
dc.identifier.doi | 10.1124/mol.108.048496 | |
dc.identifier.eissn | 1521-0111 | |
dc.identifier.issn | 0026-895X | |
dc.identifier.pubmedid | MEDLINE:18799799 | |
dc.identifier.uri | https://doi.org/10.1124/mol.108.048496 | |
dc.identifier.uri | https://repositorio.uc.cl/handle/11534/79622 | |
dc.identifier.wosid | WOS:000261003600018 | |
dc.information.autoruc | Ciencias Biológicas;Donoso M;S/I;100241 | |
dc.information.autoruc | Ciencias Biológicas;Espinoza C;S/I;142389 | |
dc.information.autoruc | Medicina;González A;S/I;52306 | |
dc.information.autoruc | Ciencias Biológicas;Huidobro-Toro J;S/I;98862 | |
dc.information.autoruc | Ciencias Biológicas;Norambuena A;S/I;94539 | |
dc.issue.numero | 6 | |
dc.language.iso | en | |
dc.nota.acceso | contenido parcial | |
dc.pagina.final | 1677 | |
dc.pagina.inicio | 1666 | |
dc.publisher | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | |
dc.revista | MOLECULAR PHARMACOLOGY | |
dc.rights | acceso restringido | |
dc.subject | LIPID RAFTS | |
dc.subject | HETERO-OLIGOMERIZATION | |
dc.subject | CARDIOVASCULAR-SYSTEM | |
dc.subject | NUCLEOTIDE RECEPTORS | |
dc.subject | EPITHELIAL-CELLS | |
dc.subject | P2X RECEPTORS | |
dc.subject | ADP RECEPTOR | |
dc.subject | CAVEOLAE | |
dc.subject | IDENTIFICATION | |
dc.subject | MICRODOMAINS | |
dc.subject.ods | 03 Good Health and Well-being | |
dc.subject.odspa | 03 Salud y bienestar | |
dc.title | P2Y(1) Receptor Activation Elicits Its Partition out of Membrane Rafts and Its Rapid Internalization from Human Blood Vessels: Implications for Receptor Signaling | |
dc.type | artículo | |
dc.volumen | 74 | |
sipa.codpersvinculados | 100241 | |
sipa.codpersvinculados | 142389 | |
sipa.codpersvinculados | 52306 | |
sipa.codpersvinculados | 98862 | |
sipa.codpersvinculados | 94539 | |
sipa.index | WOS | |
sipa.index | Scopus | |
sipa.trazabilidad | Carga SIPA;09-01-2024 |
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