Review: Ca(2+)-mobilizing receptors for ATP and UTP

Extracellular nucleotides are potent Ca2+ mobilizing agents. A variety of receptors for extracellular ATP are recognised. Some are involved in fast neuronal transmission and operate as ligand-gated ion channels. Others are involved in the paracrine or autocrine modulation of cell function. Many receptors of this type are coupled to phosphoinositide-specific phospholipase C and, in some cases, other phospholipases. One of these receptors (P2z), however, also appears to operate, at least in part, as a ligand-gated ion channel. Pharmacological data suggest that one nucleotide receptor subtype (currently designated P2U) responds selectively to either a purine nucleotide, ATP, or a pyrimidine nucleotide, UTP. According to an alternative view, ATP and UTP recognise distinct receptors. Because of the diversity of receptors for extracellular nucleotides this may be the case in some cells. Nevertheless, a G-protein coupled receptor that confers both ATP and UTP sensitivity has been cloned, expressed in cultured cell lines and sequenced. This receptor appears to have two ligand binding domains that may partially overlap. The nature of this overlap is discussed and a simple model presented. Activation of the receptor protein via one or other ligand binding domain may underlie some of the more subtle differences between the effects of ATP and UTP.