Among the various orphan G protein-coupled receptors, apelin receptor (APJ), originally
identified in the human genome as an orphan G-protein-coupled receptor, was deorphanised in
1998 with the discovery of its endogenous ligand, apelin. Apelin and APJ mRNA are widely expressed
in peripheral tissues and the central nervous system in mammals.
In this review, we discuss the characteristics, pharmacology, physiology, and pathology of the
apelin/APJ system in mammals.
Several physiological roles of the apelin/APJ system have been reported, including in homeostasis,
cardiovascular maintenance, angiogenesis, and neuroprotection. In cellular signaling, apelin has
been shown to drive the PI3K/Akt, MAPK, and PKA signaling pathways, leading to cell proliferation
and protection from excitotoxicity. Apelin is also found in breast milk; therefore, apelin is believed
to contribute to the establishment of the infant immune system. Furthermore, activation of
the apelin/APJ system is reported to restore muscular weakness associated with aging. Thus, the
apelin/APJ system represents a novel target for the prevention of several important cardiovascular
and neurodegenerative diseases and the maintenance of health during old age.