Is partial agonist activity of bucindolol dependent on the activation state of the human beta1-adrenergic receptor?
We conclude that bucindolol is a partial agonist at the human beta1-AR. In human failing myocardium, its partial agonist activity is masked by increased activation states of beta-ARs and is unmasked after in vitro pretreatment with metoprolol. Thus, the partial agonist activity of bucindolol is dependent on the activation state of the human beta1-AR.
QT and related ECG intervals are heritable traits in a large unselected population. We provide suggestive evidence for a quantitative trait locus on chromosome 3 influencing QT interval duration. Further studies are warranted to identify genes that influence QT interval variation and to determine the role of heritable factors in life-threatening QT prolongation.