Henrich M, Piper H M, Schrader J
Zentrum für Physiologie und Klinische Physiologie, Universität Düsseldorf, FRG.
Life Sci. 1987 Nov 23;41(21):2381-8. doi: 10.1016/0024-3205(87)90662-x.
Isolated metabolically stable cardiomyocytes from adult rats and mongrel dogs were used to characterize the mechanism underlying the antiadrenergic effect of adenosine. In a system not affected by cellular heterogeneity, isoproterenol (3 x 10(-9) M - 10(-5) M) in the presence of adenosine deaminase (5U/ml) dose dependently increased cellular cAMP (5-80 pmol/mg). The effect of isoproterenol (0.1 microM) was inhibited by various adenosine derivatives, the rank order of potency being in the rat: (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA) greater than 5'-N-ethylcarboxamidoadenosine (NECA) greater than S-PIA, and in the dog NECA greater than R-PIA greater than S-PIA. The cAMP increase induced by forskolin (1 microM) was attenuated in the rat by R-PIA. 8-phenyltheophylline (3 microM) antagonized the effect of R-PIA on isoproterenol-stimulated cAMP formation. Basal cAMP content was not influenced by R-PIA or NECA. Omission of adenosine deaminase from the incubation medium attenuated the isoproterenol-induced cAMP increase in the rat by about 30%. Our findings provide evidence for the presence of adenylate cyclase-coupled A1-adenosine receptors on cardiomyocytes which may mediate the antiadrenergic effect of adenosine in the heart.
来自成年大鼠和杂种犬的分离的代谢稳定的心肌细胞被用于表征腺苷抗肾上腺素能作用的潜在机制。在一个不受细胞异质性影响的系统中，在存在腺苷脱氨酶（5U/ml）的情况下，异丙肾上腺素（3×10⁻⁹M - 10⁻⁵M）剂量依赖性地增加细胞内cAMP（5 - 80 pmol/mg）。异丙肾上腺素（0.1μM）的作用被各种腺苷衍生物抑制，在大鼠中的效力顺序为：（-）-N6-（R-苯基-异丙基）-腺苷（R-PIA）＞5'-N-乙基羧酰胺腺苷（NECA）＞S-PIA，在犬中为NECA＞R-PIA＞S-PIA。在大鼠中，福斯高林（1μM）诱导的cAMP增加被R-PIA减弱。8-苯基茶碱（3μM）拮抗R-PIA对异丙肾上腺素刺激的cAMP形成的作用。基础cAMP含量不受R-PIA或NECA影响。从孵育培养基中省略腺苷脱氨酶可使大鼠中异丙肾上腺素诱导的cAMP增加减弱约30%。我们的研究结果为心肌细胞上存在与腺苷酸环化酶偶联的A1-腺苷受体提供了证据，该受体可能介导腺苷在心脏中的抗肾上腺素能作用。
