Molderings G J, Schümann H J
Pharmakologisches Institut, Universitätsklinikum Essen, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1987 Oct;336(4):403-8. doi: 10.1007/BF00164873.
In experiments on the isolated guinea-pig left atrium we tried to get more information about the intracellular signal transmission of the alpha 1-adrenoceptor. We were able to demonstrate that the cyclooxygenase inhibitors indometacin and acetylsalicylic acid enhance the positive inotropic effect of relatively low phenylephrine concentrations at an extracellular calcium concentration of 1.22 mmol/l. Preincubation with prazosin as well as an increased calcium concentration of 2.5 mmol/l abolished this effect. These observations led us to suppose that an elevated level of receptor-generated arachidonic acid, whose degradation is inhibited by the cyclooxygenase inhibitors, caused the increased contractility by releasing more calcium from the sarcoplasmic reticulum. Under these conditions also lithium caused a distinct enhancement of the positive inotropic effect evoked by alpha 1-adrenergic agonists, probably by inhibiting the degradation of the second messenger inositol trisphosphate.
在豚鼠离体左心房实验中，我们试图获取更多关于α1肾上腺素能受体细胞内信号转导的信息。我们能够证明，在细胞外钙浓度为1.22 mmol/l时，环氧合酶抑制剂吲哚美辛和乙酰水杨酸可增强相对低浓度去氧肾上腺素的正性肌力作用。用哌唑嗪预孵育以及将钙浓度提高到2.5 mmol/l可消除这种作用。这些观察结果使我们推测，环氧合酶抑制剂抑制其降解的受体生成的花生四烯酸水平升高，通过从肌浆网释放更多钙导致收缩性增加。在这些条件下，锂也可使α1肾上腺素能激动剂引起的正性肌力作用明显增强，可能是通过抑制第二信使三磷酸肌醇的降解。
