Characterization of P2X- and P2Y-purinoceptors in the rabbit hepatic arterial vasculature.
1. Responses to adenosine 5'-triphosphate (ATP) and its agonists were studied in the isolated liver of the rabbit dually perfused through the hepatic artery and the portal vein. 2. In the hepatic arterial vascular bed at basal tone, ATP and its agonists elicited vasoconstrictor responses with the rank order of potency alpha,beta-methylene ATP greater than 2-methylthio ATP greater than ATP, consistent with their action at the P2X-purinoceptor. 3. When tone was raised with noradrenaline (10(-5) M), vasodilator responses were produced with ATP and 2-methylthio ATP; alpha,beta-methylene ATP produced only further constriction. The rank order of vasodilator potency was 2-methylthio ATP greater than ATP much greater than alpha,beta-methylene ATP, consistent with their action at the P2Y-purinoceptor. 4. Methylene blue (10(-5) M) antagonized vasodilator responses to acetylcholine and ATP, but not those to adenosine or sodium nitroprusside. Addition of 8-phenyltheophylline (10(-5) M) antagonized responses to adenosine but not those to sodium nitroprusside. Responses to ATP remaining after antagonism with methylene blue were not further antagonized by 8-phenyltheophylline. 5. These results present evidence for discrete P2X- and P2Y-purinoceptors in the rabbit hepatic arterial bed which mediate vasoconstrictor and vasodilator responses respectively. 6. Vasodilatation produced by ATP was entirely due to direct action at the P2Y-purinoceptor, and not at a P1-purinoceptor following breakdown to adenosine. The antagonism of these responses by methylene blue is consistent with the view that vasodilatation by ATP takes place largely via endothelial P2Y-purinoceptors that lead to release of endothelium-derived relaxing factor. However, we cannot exclude the possibility that P2y-purinoceptors located on the vascular smooth muscle play a contributory role in ATP-induced vasodilatation.
Ralevic
V
V
Department of Anatomy & Developmental Biology, University College London.
Mathie
R T
RT
Alexander
B
B
Burnstock
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects*
D011983:Receptors, Purinergic; D009599:Nitroprusside; D000255:Adenosine Triphosphate; D000241:Adenosine; D000109:Acetylcholine; D008751:Methylene Blue; D009638:Norepinephrine