Adenosine-induced dilatation of the rabbit hepatic arterial bed is mediated by A2-purinoceptors.
1. This study was carried out in order to identify the receptor responsible for adenosine-induced dilatation of the hepatic arterial vascular bed. 2. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs-Bülbring buffer via the hepatic artery and the portal vein at constant flows of 26 and 77 ml min-1 100 g-1 liver respectively. The tone of the preparation was raised by the presence of noradrenaline in the perfusate (concentration: 10(-5) M). 3. Dose-response curves for adenosine and its analogues 5'-N-ethyl-carboxamido-adenosine (NECA), the 2-substituted NECA analogue CGS 21680C, and R- and S-N6-phenyl-isopropyl-adenosine (R- and S-PIA) were obtained after their injection into the hepatic arterial supply. 4. The order of vasodilator potency of these agents was: NECA greater than CGS 21680C greater than adenosine greater than R-PIA greater than S-PIA. Their potency, expressed relative to that of adenosine, was in the approximate ratio 10:3:1:0.3:0.1, consistent with that resulting from activation of P1-purinoceptors of the A2 sub-type (which mediate vasodilatation due to adenosine). 5. The P1-purinoceptor antagonist 8-phenyltheophylline (10(-5) M) caused significant attenuation of the vasodilatation to adenosine and analogues. 6. It is concluded that adenosine-induced dilatation of the hepatic arterial vascular bed is mediated by P1-purinoceptors of the A2 sub-type.
Mathie
R T
RT
Department of Surgery, Royal Postgraduate Medical School, London.
Alexander
B
B
Ralevic
V
V
Burnstock
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects; D066298:In Vitro Techniques; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D010627:Phenethylamines; D011983:Receptors, Purinergic; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D000109:Acetylcholine