P2Y2 receptor desensitization on single endothelial cells.
Receptor desensitization, or decreased responsiveness of a receptor to agonist stimulation, represents a regulatory process with the potential to have a significant impact on cell behavior. P2Y(2), a G-protein-coupled receptor activated by extracellular nucleotides, undergoes desensitization at many tissues, including the vascular endothelium. Endothelial cells from a variety of vascular beds are normally exposed to extracellular nucleotides released from damaged cells and activated platelets. The purpose of the present study was to compare P2Y(2) receptor desensitization observed in endothelial cells derived from bovine retina, a model of microvascular endothelium, and human umbilical vein endothelial cells (HUVECs), a model of a large blood vessel endothelium. P2Y(2) receptor desensitization was monitored by following changes in UTP-stimulated intracellular free Ca(2 +) in single cells using fura-2 microfluorometry. Both endothelial cell models exhibited desensitization of the P2Y(2) receptor after stimulation with UTP. However, the cells differed in the rate, dependence on agonist concentration, and percentage of maximal desensitization. These results suggest differential mechanisms of P2Y(2) receptor desensitization and favors heterogeneity in extracellular nucleotide activity in endothelial cells according to its vascular bed origin.
Department of Physiology, Universidad Central del Caribe, Bayamon, Puerto Rico.
Priscila
P
Sanabria
Elizabeth
E
Ross
Edgardo
E
Ramirez
Katiria
K
Colon
Millie
M
Hernandez
Hector M
HM
Maldonado
Walter I
WI
Silva
Carlos A
CA
Jimenez-Rivera
Fernando A
FA
Gonzalez
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2; D012171:Retinal Vessels / Q000166:cytology; D013050:Spectrometry, Fluorescence; D014471:Umbilical Veins / Q000166:cytology; D014544:Uridine Triphosphate / Q000494:pharmacology
D005456:Fluorescent Dyes; C546385:P2RY2 protein, human; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2; D014544:Uridine Triphosphate