Purinergic regulation of mast cell function: P2X4 receptor-mediated enhancement of allergic responses

Adenosine triphosphate (ATP) initially attracted attention as a neurotransmitter, with much research conducted on the regulation of neurotransmission in the autonomic and central nervous systems. ATP is also abundant as an energy currency in all living cells and is released into extracellular spaces by various regulated mechanisms. The role of ATP and related purine and pyrimidine nucleotides as extracellular signaling molecules in the regulation of immune cell functions has been reported as evidence for purinergic signaling and has become the focus of attention as therapeutic targets for various diseases. Mast cells (MCs) are distributed in tissues in contact with the outside environment and are the first immune cells to respond to non-microbial environmental antigens. Although extracellular ATP is known as an activator of MCs, the details remain to be investigated. Based on our series of studies, this review describes the unique features of ionotropic P2X4 receptor signals in MC functions. The role of purinergic signaling may exist in combination with various physiological, chemical and physical stimuli. The characteristics of P2X4 receptor-mediated action in MCs described in this article may provide clues to reveal the previously unknown effects induced by purinergic signaling.