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

Abstract

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 micrometer at rest), and recorded currents from arteriolar smooth muscle cells using patch-clamp techniques. Transient vasoconstrictions and rapidly inactivating currents were evoked by alpha,beta-methylene ATP (0.1-30 micrometer) and were sensitive to the P2 receptor antagonists suramin and iso-PPADS. UTP and UDP (0.1-1000 micrometer) evoked sustained suramin-sensitive vasoconstrictions. ATP (0.1-1000 micrometer) and 2-methylthioATP (2MeSATP, 300 micrometer) evoked transient vasoconstrictions followed by sustained vasodilatations. ADP application resulted in only vasodilatation (EC50 approximately 4 micrometer). Vasodilator responses to ATP, 2MeSATP or ADP were unaffected by suramin (100 micrometer). RT-PCR analysis indicated that P2X1-7 and P2Y1,2,6 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 P2X1 receptor subtype on cerebral resistance arterioles. The pharmacological properties of the pyrimidine-evoked responses suggest that a combination of P2Y2- and P2Y6-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.