Lack of adenosine A1 and dopamine D2 receptor-mediated modulation of the cardiovascular effects of the adenosine A2A receptor agonist CGS 21680.
Some behavioral and biochemical effects of the systemically administered adenosine A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) in rats are potentiated by adenosine A(1) receptor agonists and counteracted by dopamine D2 receptor agonists. In the present study we compared potentiating and antagonistic interactions between CGS 21680 and adenosine A(1) and dopamine D2 receptor agonists on motor activity and on cardiovascular responses (arterial blood pressure and heart rate). The motor-depressant effects produced by CGS 21680 (0.5 mg/kg, i.p.) were potentiated by the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA, 0.3 mg/kg, i.p.) and counteracted by the dopamine D2 receptor agonist quinpirole (0.5 mg/kg, i.p.). In contrast, neither CPA nor quinpirole significantly modified the decrease in arterial pressure or the increase in heart rate induced by CGS 21680. However, the adenosine A(2A) receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3, 3 mg/kg, i.p.) counteracted both the motor-depressant and cardiovascular effects of CGS 21680. Therefore, the effects of the systemically administered adenosine A(2A) receptor agonist CGS 21680 on cardiovascular function, in contrast to its effects on motor behavior, appear to be independent of the effects of adenosine A(1) and dopamine D2 receptor activity.
Schindler
Charles W
CW
Preclinical Pharmacology Section, Behavioral Neuroscience Branch, National Institute on Drug Abuse/NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. cschindl@helix.nih.gov
Karcz-Kubicha
Marzena
M
Thorndike
Eric B
EB
Müller
Christa E
CE
Tella
Srihari R
SR
Goldberg
Steven R
SR
Ferré
Sergi
S
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*
D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D002317:Cardiovascular Agents; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine