Heterogeneity of P2-purinoceptors in brain circulation

The existence of P2-purinoceptors in the cerebrovascular bed was examined by testing the effects of ATP and its stable analog, alpha, beta-methylene-ATP, on CBF in the unanesthetized goat as well as on isometric tension in isolated goat middle cerebral artery. When injected directly into the cerebral circulation, ATP increased and alpha, beta-methylene-ATP decreased CBF. Indomethacin did not modify either of these effects. The vasoconstrictor action of alpha, beta-methylene-ATP was reduced by nicardipine. "In vitro," both ATP and alpha, beta-methylene-ATP contracted the cerebral arteries at resting tone, but the analog was more potent than ATP. Repeated application of alpha, beta-methylene-ATP as well as indomethacin significantly reduced the ATP-induced contractions. Nicardipine inhibited both the alpha, beta-methylene-ATP- and the ATP-induced contractile response. In preconstricted arteries, ATP produced relaxation and alpha, beta-methylene-ATP induced further contraction. The relaxant response to ATP was not modified by indomethacin. These results show the existence of two subtypes of P2-purinoceptors in brain circulation: P2x, more sensitive to alpha, beta-methylene-ATP than to ATP, which elicits cerebral vasoconstriction; and P2y, sensitive to ATP, which elicits cerebral vasodilation.