Schindler Charles W, Karcz-Kubicha Marzena, Thorndike Eric B, Müller Christa E, Tella Srihari R, Goldberg Steven R, Ferré Sergi
Preclinical Pharmacology Section, Behavioral Neuroscience Branch, National Institute on Drug Abuse/NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Eur J Pharmacol. 2004 Jan 26;484(2-3):269-75. doi: 10.1016/j.ejphar.2003.11.010.
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.
全身给药的腺苷A(2A)受体激动剂2-p-(2-羧乙基)苯乙氨基-5'-N-乙基羧酰胺腺苷(CGS 21680)在大鼠体内产生的一些行为和生化效应，可被腺苷A(1)受体激动剂增强，被多巴胺D2受体激动剂抵消。在本研究中，我们比较了CGS 21680与腺苷A(1)和多巴胺D2受体激动剂在运动活性和心血管反应(动脉血压和心率)方面的增强和拮抗相互作用。CGS 21680(0.5毫克/千克，腹腔注射)产生的运动抑制效应，被腺苷A(1)受体激动剂N(6)-环戊基腺苷(CPA，0.3毫克/千克，腹腔注射)增强，被多巴胺D2受体激动剂喹吡罗(0.5毫克/千克，腹腔注射)抵消。相比之下，CPA和喹吡罗均未显著改变CGS 21680引起的动脉血压下降或心率增加。然而，腺苷A(2A)受体拮抗剂3-(3-羟丙基)-8-(间甲氧基苯乙烯基)-7-甲基-1-炔丙基黄嘌呤磷酸二钠盐(MSX-3，3毫克/千克，腹腔注射)抵消了CGS 21680的运动抑制和心血管效应。因此，全身给药的腺苷A(2A)受体激动剂CGS 21680对心血管功能的影响，与其对运动行为的影响相反，似乎独立于腺苷A(1)和多巴胺D2受体活性的影响。
