Abstract
At one time, G protein-coupled receptors were envisioned to simply relay either inhibitory or stimulatory binary signals through engaging particular G proteins. These receptors are now viewed as complex, multidimensional triggers of a variety of potential signaling cascades. This review will showcase current attempts to elucidate biased signaling and functional selectivity in tissues and organs as well as in the whole animal. In addition, it will emphasize the challenges that are inherent in attributing bias in a living system as well as offer opinions as to the manner in which these problems may be approached.