Böhm M, Brückner R, Hackbarth I, Haubitz B, Linhart R, Meyer W, Schmidt B, Schmitz W, Scholz H
J Pharmacol Exp Ther. 1984 Aug;230(2):483-92.
The antagonism between adenosine and isoprenaline on force of contraction, cyclic AMP (cAMP) and cyclic GMP (cGMP) content, adenylate cyclase activity and transmembrane action potential in isolated electrically driven atrial and ventricular muscle preparations from guinea-pig hearts was investigated. In atrial preparations adenosine added 5 min after isoprenaline decreased force of contraction. Adenosine abolished completely the positive inotropic effect of isoprenaline. Similarly, adenosine prevented the positive inotropic effect of isoprenaline when both substances were added simultaneously. In ventricular preparations adenosine also decreased the isoprenaline-induced increase in force of contraction. The effect was much smaller than it was in the atria. Adenosine reduced the isoprenaline-induced increase in force of contraction only by about 60%. Adenosine did not at all influence the positive inotropic effect of isoprenaline when both substances were added simultaneously. In both preparations the isoprenaline-induced increase in cAMP content of the intact contracting preparations was not diminished by adenosine. cGMP content remained unchanged too. Adenosine inhibited adenylate cyclase activity in broken cell preparations from both tissues. In atrial preparations the decrease in force of contraction of adenosine in the presence of isoprenaline was accompanied by a shortening of the action potential duration. In ventricular preparations adenosine failed to shorten the action potential. In conclusion, the effects of adenosine to inhibit the stimulatory action of isoprenaline on myocardial force of contraction are not due to changes in the cAMP and/or cGMP content. Instead, adenosine may inhibit a step beyond an increased cAMP level, e.g., may exert an inhibition of protein kinases. However, in the atria, but not in the ventricles, an additional direct effect of adenosine on transmembrane ion currents, most likely an increase in potassium conductance, probably is of even greater importance.
研究了腺苷与异丙肾上腺素对豚鼠心脏分离的电驱动心房和心室肌制备物收缩力、环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）含量、腺苷酸环化酶活性及跨膜动作电位的拮抗作用。在心房制备物中，异丙肾上腺素加入5分钟后再加入腺苷可降低收缩力。腺苷完全消除了异丙肾上腺素的正性肌力作用。同样，当两种物质同时加入时，腺苷也可阻止异丙肾上腺素的正性肌力作用。在心室制备物中，腺苷也可降低异丙肾上腺素诱导的收缩力增加。该作用比在心房中要小得多。腺苷仅使异丙肾上腺素诱导的收缩力增加降低约60%。当两种物质同时加入时，腺苷对异丙肾上腺素的正性肌力作用毫无影响。在两种制备物中，腺苷均未减弱异丙肾上腺素诱导的完整收缩制备物中cAMP含量的增加。cGMP含量也保持不变。腺苷抑制了两种组织破碎细胞制备物中的腺苷酸环化酶活性。在心房制备物中，在存在异丙肾上腺素的情况下，腺苷引起的收缩力降低伴随着动作电位时程的缩短。在心室制备物中，腺苷未能缩短动作电位。总之，腺苷抑制异丙肾上腺素对心肌收缩力刺激作用的效应并非由于cAMP和/或cGMP含量的变化。相反，腺苷可能抑制了cAMP水平升高之后的一个步骤，例如，可能对蛋白激酶发挥抑制作用。然而，在心房而非心室中，腺苷对跨膜离子电流的额外直接作用，很可能是钾电导增加，可能更为重要。
