Scholarlink

<p>N<sup>6</sup>-(R)-Phenylisopropyladenosine (R-PIA), an agonist at A<sub>1</sub>-adenosine receptors, alone exerts negative inotropic effects (NIE) in the human atrium. This NIE is augmented in the presence of cAMP-increasing agonists like phosphodiesterase inhibitors (cilostamide, rolipram) or a direct activator of adenylyl cyclase (forskolin). Cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). We hypothesized that cantharidin would attenuate this NIE of R-PIA in the presence of cilostamide or forskolin. During open heart surgery (patients were suffering from severe coronary heart disease), isolated human atrial preparations (HAP) were obtained. These HAP were mounted in organ baths and electrically stimulated (1 Hz). For comparison, we studied isolated electrically stimulated (1 Hz) left atrial preparations (LA) from wild type mice. We noted that R-PIA exerted negative inotropic effects in LA and HAP in the presence of cilostamide or rolipram and forskolin that were attenuated by cantharidin. We hypothesize that R-PIA in the presence of phosphodiesterase inhibitors or forskolin stimulates PP in the human atrium. Hence, R-PIA acts, at least in part, by stimulating PP in HAP.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Inhibition of protein phosphatases attenuates A1-adenosine receptor-stimulation induced negative inotropic effects of cAMP-increasing agents in the isolated human atrium

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月5日

查看全文
  • Rebecca Schwarz,
  • Britt Hofmann,
  • Ulrich Gergs,
  • Joachim Neumann

摘要

N6-(R)-Phenylisopropyladenosine (R-PIA), an agonist at A1-adenosine receptors, alone exerts negative inotropic effects (NIE) in the human atrium. This NIE is augmented in the presence of cAMP-increasing agonists like phosphodiesterase inhibitors (cilostamide, rolipram) or a direct activator of adenylyl cyclase (forskolin). Cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). We hypothesized that cantharidin would attenuate this NIE of R-PIA in the presence of cilostamide or forskolin. During open heart surgery (patients were suffering from severe coronary heart disease), isolated human atrial preparations (HAP) were obtained. These HAP were mounted in organ baths and electrically stimulated (1 Hz). For comparison, we studied isolated electrically stimulated (1 Hz) left atrial preparations (LA) from wild type mice. We noted that R-PIA exerted negative inotropic effects in LA and HAP in the presence of cilostamide or rolipram and forskolin that were attenuated by cantharidin. We hypothesize that R-PIA in the presence of phosphodiesterase inhibitors or forskolin stimulates PP in the human atrium. Hence, R-PIA acts, at least in part, by stimulating PP in HAP.