Coexpression of P2Yand P2UReceptors on Aortic Endothelial Cells
Copyright policy )Coexpression of P2Yand P2UReceptors on Aortic Endothelial Cells
AbstractDepending on the vascular bed considered, the actions of ATP on the endothelium are mediated by either P2Yor P2Ureceptors. The two types of receptors seem to coexist on bovine aortic endothelial cells, where they are both coupled to phospholipase C. In this study, we have investigated whether they are truly coexpressed on the same cells and whether their signaling pathways diverge beyond phospholipase C activation. Measurements of [Ca2+]iin single cells showed that almost all bovine aortic endothelial cells are responsive to both 2-methylthio-ATP (2MeSATP), an agonist of P2Yreceptors, and UTP, an agonist of P2Ureceptors. UTP stimulated the release of prostacyclin from freshly isolated bovine aortic endothelial cells, even when they were exposed to cycloheximide at the time of their collection: this indicates that P2Ureceptors must already be expressed on endothelial cells in situ and do not appear during cell culture. The time course of inositol phosphate (InsP) accumulation and the relative proportion of Ins(1,4,5)P3, Ins(1,3,4,5)P4, and Ins(1,3,4)P3were similar in cells stimulated by 2MeSATP or UTP. UTP and 2MeSATP both stimulated the hydrolysis of phosphatidylcholine by phospholipase D, as reflected by the release of [3H]choline from prelabeled cells. The responses to both agents were blocked after downregulation of protein kinase C, resulting from a prolonged exposure to phorbol 12-myristate 13-acetate: this blockade occurred at a step distal to phospholipase C activation. A single difference between the two pathways has been identified: the effect of 2MeSATP on InsP3was significantly more inhibited after a short exposure to phorbol 12-myristate 13-acetate than that of UTP. This discrepancy is consistent with the involvement of distinct G proteins in the activation of phospholipase C by P2Yand P2Ureceptors.
- Université Libre de Bruxelles Belgium
Protein Kinase C -- metabolism, Adenosine Triphosphate -- pharmacology, Epoprostenol -- metabolism, Thionucleotides -- pharmacology, Inositol Phosphates, Uridine Triphosphate, Uridine Triphosphate -- pharmacology, Choline, Adenosine Triphosphate, Isomerism, Vascular -- cytology, Receptors, Aorta -- metabolism, Animals, Purinergic P2 -- metabolism, Endothelium, Adenosine Triphosphate -- analogs & derivatives, Aorta -- cytology, Intracellular Membranes -- metabolism, Aorta, Protein Kinase C, Receptors, Purinergic P2, Purinergic P2 -- classification, Inositol Phosphates -- metabolism, Intracellular Membranes, Sciences bio-médicales et agricoles, Thionucleotides, Epoprostenol, Vascular -- metabolism, Inositol Phosphates -- chemistry, Choline -- metabolism, Calcium -- metabolism, Calcium, Cattle, Female, Endothelium, Vascular, Signal Transduction
Protein Kinase C -- metabolism, Adenosine Triphosphate -- pharmacology, Epoprostenol -- metabolism, Thionucleotides -- pharmacology, Inositol Phosphates, Uridine Triphosphate, Uridine Triphosphate -- pharmacology, Choline, Adenosine Triphosphate, Isomerism, Vascular -- cytology, Receptors, Aorta -- metabolism, Animals, Purinergic P2 -- metabolism, Endothelium, Adenosine Triphosphate -- analogs & derivatives, Aorta -- cytology, Intracellular Membranes -- metabolism, Aorta, Protein Kinase C, Receptors, Purinergic P2, Purinergic P2 -- classification, Inositol Phosphates -- metabolism, Intracellular Membranes, Sciences bio-médicales et agricoles, Thionucleotides, Epoprostenol, Vascular -- metabolism, Inositol Phosphates -- chemistry, Choline -- metabolism, Calcium -- metabolism, Calcium, Cattle, Female, Endothelium, Vascular, Signal Transduction
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