G-protein independent signaling induced by be-ta blocker and the significance of the signaling.

美托洛尔是β-1肾上腺素能受体的特异性拮抗剂之一。我们意外地发现，长期服用美托洛尔会导致小鼠心脏纤维化。美托洛尔的这种纤维化信号是由β-1肾上腺素能受体以G蛋白非依赖性的方式介导的，需要ERK1的激活。我们还证明了信号通路依赖于β-arrestin2和GRK5。事实上，当美托洛尔被给予β-arrestin2或GRK5缺陷小鼠时，并没有观察到心脏纤维化。

Metoprolol is one of antagonists specific for the β1 adrenergic receptor. We accidentally found that long-term administration of metoprolol induced cardiac fibrosis in mice. This fibrosis signal by metoprolol is mediated by β1 adrenergic receptor in a G protein-independent fashion and requires ERK activation. We also demonstrate that the signal pathway depends on β-arrestin2 and GRK5. Indeed, the cardiac fibrosis was not observed when the metoprolol was administered to β-arrestin2 or GRK5 deficient mice.