Facilitation of Neurotransmitter and Hormone Release by P2X Purinergic Receptors

Abstract

Nucleotides are emerging as ubiquitous family of extracellular signaling molecules. Their effects are mediated through a specific class of plasma membrane receptors called purinergic P2 receptors that, according to the molecular structure, are further subdivided into two subfamilies: P2Y and P2X. Specifically, P2X receptors (P2XRs) are ligand-gated ion channels, whereas P2Y receptors (P2YRs) belong to the superfamily of G-protein-coupled receptors. Purinergic P2XRs are expressed in a wide range of organisms from amoeba to humans (Fountain et al., 2007). In mammals, seven P2X subunits (termed P2X1-7) have been found (North, 2002). These receptors appeared early in evolution and have a widespread distribution on many neurons and non-neuronal cells. The P2XRs comprise the family of trimeric channels that use the energy of extracellular ATP binding to initiate a depolarizing flux of cations, including calcium, through the pore of channels. The extracellular actions of ATP are terminated by ectonucleotidases, leading to the generation of ADP, a primary agonist for some P2YRs, and adenosine, the common agonist for adenosine subtypes of receptor (Ralevic and Burnstock, 1998). Substantial progress has been made in elucidating the roles these receptors play under physiological and pathological conditions and in our understanding of the functional, structural, and pharmacological properties of seven P2X receptor subtypes. Purinergic signaling is involved in several basic physiological responses such as embryonic and stem cell development, pain sensation, regulation of renal blood flow, inflammatory responses, auditory neurotransmission etc., wh