中枢和外周腺苷受体在腹腔注射腺苷A1和A2A亚型受体激动剂后心血管反应中的作用。
Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A1 and A2A subtype receptor agonists.
作者信息
Schindler Charles W, Karcz-Kubicha Marzena, Thorndike Eric B, Müller Christa E, Tella Srihari R, Ferré Sergi, Goldberg Steven R
机构信息
Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Department of Health and Human Services, National Institutes of Health/National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USA.
出版信息
Br J Pharmacol. 2005 Mar;144(5):642-50. doi: 10.1038/sj.bjp.0706043.
Abstract
- The cardiovascular effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the adenosine A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate. 2. Intraperitoneal (i.p.) injections of the adenosine A1 receptor agonist CPA led to dose-dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg(-1) CPA were antagonized by i.p. injections of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT), but not by i.p. injections of the adenosine A2A receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8-sulfophenyltheophylline (8-SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardiovascular effects of CPA. 3. The adenosine A2A agonist CGS 21680 given i.p. produced a dose-dependent decrease in blood pressure and an increase in heart rate. These effects of 0.5 mg kg(-1) CGS 21680 were antagonized by i.p. injections of the adenosine A2A receptor antagonist MSX-3, but not by i.p. injections of the antagonists CPT, 8-SPT or caffeine. 4. Central administration (intracerebral ventricular) of CGS 21680 produced an increase in heart rate, but no change in blood pressure. MSX-3 given i.p. antagonized the effects of the central injection of CGS 21680. 5. These results suggest that adenosine A1 receptor agonists produce decreases in blood pressure and heart rate that are mediated by A1 receptors in the periphery, with little or no contribution of central adenosine A1 receptors to those effects. 6. The heart rate increasing effect of adenosine A2A agonists appears to be mediated by adenosine A2A receptors in the central nervous system. The blood pressure decreasing effect of adenosine A2A agonists is most probably mediated in the periphery.
摘要
- 研究了腺苷A1受体激动剂N6-环戊基腺苷（CPA）和腺苷A2A受体激动剂2-对-（2-羧乙基）苯乙氨基-5'-N-乙基羧酰胺腺苷（CGS 21680）对植入遥测发射器以测量血压和心率的大鼠的心血管作用。2. 腹腔注射腺苷A1受体激动剂CPA导致血压和心率呈剂量依赖性下降。0.3 mg kg(-1) CPA的这些作用被腹腔注射腺苷A1受体拮抗剂8-环戊基-1,3-二甲基黄嘌呤（CPT）所拮抗，但不被腹腔注射腺苷A2A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）所拮抗。腹腔注射外周作用的非选择性腺苷拮抗剂8-磺苯基茶碱（8-SPT）和所谓的非选择性腺苷拮抗剂咖啡因也拮抗了CPA的心血管作用。3. 腹腔注射腺苷A2A激动剂CGS 21680导致血压呈剂量依赖性下降和心率增加。0.5 mg kg(-1) CGS 21680的这些作用被腹腔注射腺苷A2A受体拮抗剂MSX-3所拮抗，但不被腹腔注射拮抗剂CPT、8-SPT或咖啡因所拮抗。4. 向脑室内中枢给药CGS 21680导致心率增加，但血压无变化。腹腔注射MSX-3拮抗了中枢注射CGS 21680的作用。5. 这些结果表明，腺苷A1受体激动剂导致血压和心率下降，这是由外周的A1受体介导的，中枢腺苷A1受体对这些作用的贡献很小或没有贡献。6. 腺苷A2A激动剂的心率增加作用似乎是由中枢神经系统中的腺苷A2A受体介导的。腺苷A2A激动剂的血压下降作用很可能在外周介导。
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