Hattori Y, Levi R
J Pharmacol Exp Ther. 1984 Nov;231(2):215-23.
Adenosine is known to attenuate the positive inotropic and chronotropic effects of norepinephrine and histamine by reducing cyclic AMP accumulation. We assessed whether adenosine, while inhibiting the cardiac responses mediated by beta and H2 receptors, leaves unmodified the responses mediated by alpha and H1 receptors. In isolated cardiac preparations from the guinea pig, adenosine antagonized the positive inotropic effect of histamine more than that of norepinephrine. This most likely occurred because, by attenuating H2 and beta responses, adenosine unmasked the H1-negative and alpha-1-positive components of the inotropic effects of histamine and norepinephrine. Consistent with this hypothesis, the pure H2 agonist impromidine appeared to be antagonized by adenosine less than histamine, and norepinephrine less than isoproterenol. In addition, adenosine antagonized the positive inotropic effect of norepinephrine in the presence of the alpha-1 blocker prazosin, whereas it did not affect the inotropic effect of phenylephrine. In the papillary muscle depolarized by 22 mM K+, adenosine antagonized the restoration of contractile responses induced by histamine or norepinephrine. This action of adenosine was reversed by the phosphodiesterase inhibitor papaverine and by the adenylate cyclase activator forskolin, suggesting that adenosine attenuates beta and H2 responses by suppressing the cyclic AMP-dependent facilitation of Ca++ influx promoted by the two amines. Our data indicate that adenosine selectively attenuates H2 and beta but not alpha and H1 responses. Thus, when catecholamines, histamine and adenosine are released together, as in myocardial ischemia, in addition to their individual effects, negative inotropism, decreased impulse conduction velocity and coronary constriction (i.e., H1- and alpha-mediated responses) may result from the adenosine-histamine-norepinephrine interaction.
已知腺苷可通过减少环磷酸腺苷（cAMP）的积累来减弱去甲肾上腺素和组胺的正性肌力作用和变时作用。我们评估了腺苷在抑制由β受体和H2受体介导的心脏反应时，是否对由α受体和H1受体介导的反应没有影响。在豚鼠的离体心脏标本中，腺苷对组胺正性肌力作用的拮抗作用比对去甲肾上腺素的更强。这很可能是因为，通过减弱H2和β反应，腺苷揭示了组胺和去甲肾上腺素正性肌力作用中的H1负性和α-1正性成分。与该假设一致，纯H2激动剂英普咪定似乎比组胺受腺苷的拮抗作用小，而去甲肾上腺素比异丙肾上腺素受腺苷的拮抗作用小。此外，在存在α-1阻滞剂哌唑嗪的情况下，腺苷拮抗去甲肾上腺素的正性肌力作用，而它不影响去氧肾上腺素的正性肌力作用。在由22 mM钾离子使乳头肌去极化的情况下，腺苷拮抗组胺或去甲肾上腺素诱导的收缩反应的恢复。腺苷的这一作用被磷酸二酯酶抑制剂罂粟碱和腺苷酸环化酶激活剂福斯可林逆转，提示腺苷通过抑制这两种胺促进的环磷酸腺苷依赖性钙内流增强作用来减弱β和H2反应。我们的数据表明，腺苷选择性地减弱H2和β反应，但不减弱α和H1反应。因此，当儿茶酚胺、组胺和腺苷一起释放时，如在心肌缺血时，除了它们各自的作用外，负性肌力作用、冲动传导速度降低和冠状动脉收缩（即H1和α介导的反应）可能是由腺苷-组胺-去甲肾上腺素相互作用导致的。
