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.
Shirahase
H
H
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Usui
H
H
Shimaji
H
H
Kurahashi
K
K
Fujiwara
M
M
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D014661:Vasoconstriction
D008689:Methacrylates; D011983:Receptors, Purinergic; D013928:Thromboxane A2; C049855:ONO 3708; D000255:Adenosine Triphosphate; D009543:Nifedipine; C034364:ozagrel; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D001241:Aspirin; D002118:Calcium