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.
Torregrosa
G
G
Centro de Investigación, Hospital La Fe, Valencia, Spain.
Miranda
F J
FJ
Salom
J B
JB
Alabadí
J A
JA
Alvarez
C
C
Alborch
E
E
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006041:Goats; D007213:Indomethacin / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D007213:Indomethacin