Comparison of P2 receptor subtypes producing dilation in rat intracerebral arterioles

Abstract

Background and Purpose - P2 receptors are important regulators of cerebrovascular tone. However, there is functional heterogeneity of P2Y receptors along the vascular tree, and the functionality of P2Y receptors in small arterioles has not been studied in detail. We investigated the effects of activating P2Y1 and P2Y2 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 P2 receptor agonist ATP in addition to ADP-β-S (P2Y1-selective) and ATP-γ-S (P2Y2-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 P2Y1 receptor antagonist) blocked ADP-β-S- but not ATP-γ-S -induced dilation and affected the ATP-mediated dilation at low concentrations. Nω-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 P2Y1 and P2Y2 receptors are functionally present in cerebral arterioles. ATP stimulates P2Y1 receptors at low concentrations, while high concentrations of ATP activate P2Y2 in addition to P2Y1 receptors. Nitric oxide is involved in P2Y1 but not P2Y2 receptor activation. Potassium channels play an important role in the regulation of P2Y receptor-mediated dilation.