Heterogeneity of P₂-Purinoceptors in Brain Circulation

Abstract

Summary:The existence of P2-purinoceptors in the cere brovascular bed was examined by testing the effects of ATP and its stable analog, u,p-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, A TP increased and u,p-methylene-ATP decreased CBF. Indomethacin did not modify either of these effects. The vasoconstrictor action of u,p-methylene-ATP was reduced by nicar dipine. "In vitro," both ATP and u,p-methylene-ATP contracted the cerebral arteries at resting tone, but the analog was more potent than A TP. 572cantly reduced the ATP-induced contractions. Nicar dipine inhibited both the u,p-methylene-ATP-and the ATP-induced contractile response. In preconstricted ar teries, ATP produced relaxation and u,p-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 u,P methylene-ATP than to ATP, which elicits cerebral vas oconstriction; and P2y, sensitive to ATP, which elicits cerebral vasodilation.

Purinergic Signaling and Blood Vessels in Health and Disease

“…a,b-MeATP produced potent contractions of goat middle cerebral artery (Torregrosa et al, 1990a), suggesting mediation via P2X 1 receptors. UTP and UDP induced a long-lasting contraction of isolated brain arteries in humans (Urquilla et al, 1978) and dogs (Shirasawa et al, 1983).…”