Background and Purpose--P₂ 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 P₂ receptor agonist ATP in addition to ADP--S (P_2Y1-selective) and ATP--S (P_2Y2-selective) and inhibitors of signaling pathways.

Results--Extraluminal application of ATP--S and ADP--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--S- but not ATP--S-induced dilation and affected the ATP-mediated dilation at low concentrations. N-Monomethyl-L-arginine partially inhibited the dilation of ATP and ADP--S but not ATP--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.