Receptor subtypes mediating adenosine-induced dilation of cerebral arterioles.
The purpose of this study was to investigate the receptor subtypes that mediate the dilation of rat intracerebral arterioles elicited by adenosine. Penetrating arterioles were isolated from the rat brain, cannulated with the use of a micropipette system, and luminally pressurized to 60 mmHg. Both adenosine and the A2A receptor-selective agonist CGS-21680 induced dose-dependent vasodilation (-logEC(50): 6.5 +/- 0.2 and 8.6 +/- 0.3, respectively). However, adenosine, which is capable of activating both A2A and A2B receptors, caused a greater maximal dilation than CGS-21680. The A2A receptor-selective antagonist ZM-241385 (0.1 microM) only partially inhibited the dilation induced by adenosine but almost completely blocked CGS-21680-induced dilation. Neither 8-cyclopentyl-1,3-dipropylxanthine (0.1 microM), an A1 receptor-selective antagonist, nor MRS-1191 (0.1 microM), an A3 receptor-selective antagonist, attenuated adenosine dose responses. Moreover, ZM-241385 had no effect on the dilation induced by ATP (10 microM) or acidic (pH 6.8) buffer. We concluded that the A2A receptor subtype mediates adenosine-induced dilation of intracerebral arterioles in the rat brain. Furthermore, our results suggest that A2B receptors may also participate in the dilation response to adenosine.
Ngai
A C
AC
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington 98104, USA. ngai@u.washington.edu
Coyne
E F
EF
Meno
J R
JR
West
G A
GA
Winn
H R
HR
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D010627:Phenethylamines; D011799:Quinazolines; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000255:Adenosine Triphosphate; D000241:Adenosine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine