A membrane network of receptors and enzymes for adenine nucleotides and nucleosides.

Most cells express more than one receptor plus degrading enzymes for adenine nucleotides or nucleosides, and cellular responses to purines are rarely compatible with the actions of single receptors. Therefore, these receptors are viewed as components of a combinatorial receptor web rather than self-dependent entities, but it remained unclear to what extent they can associate with each other to form signalling units. P2Y(1), P2Y(2), P2Y(12), P2Y(13), P2X(2), A(1), A(2A) receptors and NTPDase1 and -2 were expressed as fluorescent fusion proteins which were targeted to membranes and signalled like the unlabelled counterparts.

Autoregulation in PC12 cells via P2Y receptors: Evidence for non-exocytotic nucleotide release from neuroendocrine cells.

Nucleotides are released not only from neurons, but also from various other types of cells including fibroblasts, epithelial, endothelial and glial cells. While ATP release from non-neural cells is frequently Ca(2+) independent and mostly non-vesicular, neuronal ATP release is generally believed to occur via exocytosis. To evaluate whether nucleotide release from neuroendocrine cells might involve a non-vesicular component, the autocrine/paracrine activation of P2Y(12) receptors was used as a biosensor for nucleotide release from PC12 cells.

Functions of neuronal P2Y receptors.

Within the last 15 years, at least eight different G protein-coupled nucleotide receptors, i.e., P2Y receptors, have been characterized by molecular means.

Presynaptic inhibition via a phospholipase C- and phosphatidylinositol bisphosphate-dependent regulation of neuronal Ca2+ channels.

Presynaptic inhibition of transmitter release is commonly mediated by a direct interaction between G protein betagamma subunits and voltage-activated Ca2+ channels. To search for an alternative pathway, the mechanisms by which presynaptic bradykinin receptors mediate an inhibition of noradrenaline release from rat superior cervical ganglion neurons were investigated. The peptide reduced noradrenaline release triggered by K+-depolarization but not that evoked by ATP, with Ca2+ channels being blocked by Cd2+.