Endothelium-independent and endothelium-dependent contractions mediated by P2X- and P2Y-purinoceptors in canine basilar arteries

Both alpha, beta-methylene ATP and beta, gamma-methylene ATP (P2X selective agonists) were shown to induce transient contraction in intact and endothelium-removed preparations of canine basilar arteries. 2-Methylthio ATP (a P2Y selective agonist) caused transient contraction of intact arteries and this response was nearly abolished by removal of the endothelium. In the presence of alpha, beta-methylene ATP (10(-6) M), the endothelium-independent contractions induced by alpha, beta-methylene ATP itself (10(-6) M) and by beta, gamma-methylene ATP (10(-5) M) were both abolished. The endothelium-dependent contraction induced by 2-methylthio ATP (10(-7) M) was not attenuated by alpha, beta-methylene ATP. The contraction induced by 2-methylthio ATP (10(-7) M) was attenuated markedly by reactive blue 2 (a P2Y antagonist) (3 x 10(-6) M), aspirin (5 x 10(-5) M), OKY-046 (thromboxane A2 synthetase inhibitor) (10(-5) M) and ONO-3708 (thromboxane A2 antagonist) (10(-8) M). However, these agents did not affect the endothelium-independent contraction induced by alpha, beta-methylene ATP (10(-6) M). Neither TMK-777 (a 5-lipoxygenase inhibitor) (10(-7) M) nor superoxide dismutase (100 U/ml) plus catalase (1,000 U/ml) affected either contraction. The present experiments demonstrate that P2X-purinoceptors mediate endothelium-dependent contraction in the canine basilar artery, and that the endothelium-derived contracting factor in this system is probably thromboxane A2.