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 cha nges 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 evoke d by alpha,beta-methylene ATP (0.1-30 mu M) and were sensitive to the P2 re ceptor antagonists suramin and iso-PRADS. 3. UTP and UDP (0.1 - 1000 mu M) evoked sustained suramin-sensitive vasocon strictions. 4. ATP (0.1-1000 mu M) and 2-methylthioATP (2MeSATP, 300 mu M) evoked trans ient vasoconstrictions followed by sustained vasodilations. ADP application resulted in only vasodilatation (EC50 similar to 4 mu M). Vasodilator resp onses 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 amplif ied from the pial sheet. Our results provide direct evidence for the presen ce of functional P2X receptors with a phenotype resembling the P2X(1) recep tor subtype on cerebral resistance arterioles. The pharmacological properti es of the pyrimidine-evoked responses suggest that a combination of P2Y(2)- and P2Y(6)-like receptors are responsible for the sustained vasoconstricti ons. It is therefore likely that the nucleotides and their associated recep tors are involved in a complicated regulatory system to control cerebral bl ood pressure.