Comparison of P 2 Receptor Subtypes Producing Dilation in Rat Intracerebral Arterioles

Abstract

Background and Purpose— P ₂ receptors are important regulators of cerebrovascular tone. However, there is functional heterogeneity of P _2Y receptors along the vascular tree, and the functionality of P _2Y receptors in small arterioles has not been studied in detail. We investigated the effects of activating P _2Y1 and P _2Y2 receptors and their underlying dilator mechanisms in rat intracerebral arterioles. Methods— We used computer-aided videomicroscopy to measure diameter responses from isolated and pressurized rat penetrating arterioles (39.9±1.2 μm) to the natural P ₂ receptor agonist ATP in addition to ADP-β-S (P _2Y1 -selective) and ATP-γ-S (P _2Y2 -selective) and inhibitors of signaling pathways. Results— Extraluminal application of ATP-γ-S and ADP-β-S initiated a biphasic response (initial constriction followed by the secondary dilation) similar to ATP-induced responses. Pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid (0.1 mmol/L; a P _2Y1 receptor antagonist) blocked ADP-β-S- but not ATP-γ-S-induced dilation and affected the ATP-mediated dilation at low concentrations. N ^ω -Monomethyl- l -arginine partially inhibited the dilation of ATP and ADP-β-S but not ATP-γ-S. High K ⁺ saline suppressed the dilation of all agonists. Indomethacin had no effect. Conclusions— Both P _2Y1 and P _2Y2 receptors are functionally present in cerebral arterioles. ATP stimulates P _2Y1 receptors at low concentrations, while high concentrations of ATP activate P _2Y2 in addition to P _2Y1 receptors. Nitric oxide is involved in P _2Y1 but not P _2Y2 receptor activation. Potassium channels play an important role in the regulation of P _2Y receptor-mediated dilation.