Comparison of P2 receptor subtypes producing dilation in rat intracerebral arterioles

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 mum) to the natural P-2 receptor agonist ATP in addition to ADP-beta-S (P-2Y1-selective) and ATP-gamma-S (P-2Y2-selective) and inhibitors of signaling pathways. Results-Extraluminal application of ATP-gamma-S and ADP-beta-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-beta-S- but not ATP-gamma-S-induced dilation and affected the ATP-mediated dilation at low concentrations. N-omega-Monomethyl-L-arginine partially inhibited the dilation of ATP and ADP-beta-S but not ATP-gamma-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.