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Endothelial P2Y1 receptor desensitizes by protein kinase C‐dependent mechanisms in rat small mesenteric arteries
Author(s) -
RodriguezRodriguez Rosalia,
Garland Christopher J,
Dora Kim A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.636
Subject(s) - agonist , vasodilation , receptor , mesenteric arteries , endocrinology , p2y receptor , protein kinase c , medicine , endothelium , desensitization (medicine) , chemistry , perfusion , kinase , artery , biochemistry
Extracellular nucleotides evoke EDHF‐type vasodilatation in resistance arteries by stimulating P2Y 1 and P2Y 2 receptors on the vascular endothelium. These G‐protein coupled receptors can desensitize upon prolonged exposure. Our aim was to determine the extent and nature of this desensitization in isolated and pressurized rat small mesenteric arteries. Luminal perfusion with the non‐hydrolyzable selective P2Y 1 agonist, ADPβS (3μM) evoked vasodilatation that desensitized rapidly over time, and at this time, co‐perfusion with either ADP (1μM, P2Y 1 receptor agonist) or UTP (3μM, P2Y 2 receptor agonist) did not evoke further dilatation. Evaluation of the homologous desensitization of P2Y 1 receptors showed that luminal incubation with the PKC inhibitor BIS I (1μM) tended to augment dilatation to ADP (10nM‐1μM) and ADPβS (0.1–3μM). In separate experiments, P2Y 1 receptor activation during luminal perfusion of ADPβS increased endothelial cell [Ca 2+ ] i in pressurized arteries, which also desensitized. This desensitization was also significantly reduced by BIS‐I. These data demonstrate the involvement of PKC in the desensitization of endothelial P2Y 1 and P2Y 2 receptors in pressurized rat mesenteric arteries, although a role for other protein kinases cannot be discarded. The Wellcome Trust, UK, supported this work