P2 purinoceptor-mediated control of rat cerebral (pial) microvasculature; contribution of P2X and P2Y receptors

1. Purine and pyrimidine nucleotides evoke changes in the vascular tone of medium to large cerebral vessels through the activation of P2 purinoceptors. We have applied P2 receptor drugs to rat pial arterioles and measured changes in arteriole diameter (o.d. 40-84 mu m at rest), and recorded currents from arteriolar smooth muscle cells using patch-clamp techniques. 2. Transient vasoconstrictions and rapidly inactivating currents were evoked by alpha,beta-methylene ATP (0.1-30 mu M) and were sensitive to the P2 receptor antagonists suramin and iso-PRADS. 3. UTP and UDP (0.1 - 1000 mu M) evoked sustained suramin-sensitive vasoconstrictions. 4. ATP (0.1-1000 mu M) and 2-methylthioATP (2MeSATP, 300 mu M) evoked transient vasoconstrictions followed by sustained vasodilations. ADP application resulted in only vasodilatation (EC50 similar to 4 mu M). Vasodilator responses to ATP, 2MeSATP or ADP were unaffected by suramin (100 mu M). 5. RT-PCR analysis indicated that P2X(1-7) and P2Y(1,2,6) RNA can be amplified from the pial sheet. Our results provide direct evidence for the presence of functional P2X receptors with a phenotype resembling the P2X(1) receptor subtype on cerebral resistance arterioles. The pharmacological properties of the pyrimidine-evoked responses suggest that a combination of P2Y(2)- and P2Y(6)-like receptors are responsible for the sustained vasoconstrictions. It is therefore likely that the nucleotides and their associated receptors are involved in a complicated regulatory system to control cerebral blood pressure.