Modification of cardiovascular response of adenosine A2 receptor agonist by adenylate cyclase in the spinal cord of rats.
This study was performed to investigate the influence of spinal adenosine A2 receptors on the central regulation of blood pressure (BP) and heart rate (HR), and to define whether its mechanism is mediated by adenylate cyclase or guanylate cyclase. Intrathecal (i.t.) administration of drugs at the thoracic level were performed in anesthetized, artificially ventilated male Sprague-Dawley rats. Injection (i.t.) of adenosine A2 receptor agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 3 nmol) produced a dose dependent decrease of BP and HR. Pretreatment with adenylate cyclase inhibitor, MDL-12,330, attenuated the depressor and bradycardiac effects of CPCA (2 nmol), but not with guanylate cyclase inhibitor, LY-83,583. These results suggest that adenosine A2 receptor in the spinal cord plays an inhibitory role in the central cardiovascular regulation and that the depressor and bradycardiac actions are mediated by adenylate cyclase.
Koh
H C
HC
Department of Pharmacology, College of Medicine, Hanyang University, Seoul, South Korea.
Lee
T K
TK
Kang
J S
JS
Lee
C H
CH
Lee
H
H
Paik
D J
DJ
Shin
I C
IC
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000494:pharmacology* / Q000502:physiology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006339:Heart Rate / Q000187:drug effects; D007097:Imines / Q000494:pharmacology; D007278:Injections, Spinal; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D013116:Spinal Cord / Q000201:enzymology*; D013909:Thorax
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D007097:Imines; D058906:Purinergic P1 Receptor Agonists; C024311:N-cyclopropyl adenosine-5'-carboxamide; C014925:RMI 12330A; C041715:6-anilino-5,8-quinolinedione; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000241:Adenosine