INVITED REVIEW Molecular properties of P2X receptors

Abstract P2X receptors for adenosine tri-phosphate (ATP) are a distinct family of ligand-gated cation channels with two transmembrane domains, intracellular amino and carboxy termini and a large extracellular ligand binding loop. Seven genes (P2X 1-7 ) have been cloned and the channels form as either homo or heterotrimeric channels giving rise to a wide range of phenotypes. This review aims to give an account of recent work on the molecular basis of the properties of P2X receptors. In particular, to consider emerging information on the assembly of P2X receptor subunits, channel regulation and desensitisation, targeting, the molecular basis of drug action and the functional contribution of P2X receptors to physiological processes

Contribution of P2Y1 receptors to ADP signalling in mouse spinal cord cultures

Mixed neuronal and glial cell spinal cord cultures from neonates express ADP sensitive P2Y1,12&13 receptors. ADP (10 μM) evoked increases in intracellular calcium that were essentially abolished by the P2Y1 receptor antagonist MRS2179 (10 μM), responses were also absent in preparations from P2Y1 receptor deficient mice however UTP (100 μM) evoked calcium rises were unaffected. ADP also evoked a robust increase in extracellular signal-regulated protein kinase (ERK) phosphorylation that was of similar magnitude in the cultures from wild type and P2Y1 receptor deficient mice. These results suggest that ADP acts through P2Y1 receptors to mediate an increase in intracellular calcium but not to stimulate ERK phosphorylation in the spinal cord

Evidence for P2Y(1), P2Y(2), P2Y(6) and atypical UTP-sensitive receptors coupled to rises in intracellular calcium in mouse cultured superior cervical ganglion neurons and glia

1. P2Y receptors are expressed in the nervous system and are involved in calcium signalling in neurons and glia. In the superior cervical ganglion (SCG), RT–PCR analysis indicated the presence of P2Y(1,2&6) receptors. Rises in intracellular calcium in response to P2Y receptor stimulation were determined from adult mouse cultured SCG neurons and glia. 2. ADP evoked suramin (100 μM)- and pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS, 30 μM)-sensitive rises in intracellular calcium in ∼80% of SCG neurons (EC(50)∼20 μM). ADP-evoked responses were abolished in neurons from P2Y(1) receptor-deficient mice (responses to UTP were unaffected). 3. The pyrimidines UTP (EC(50)∼85 μM) and UDP (EC(50)>90 μM) evoked PPADS- and suramin-sensitive responses in ∼70 and ∼20% of SCG neurons, respectively. 4. In SCG glial cells, ADP (EC(50)∼30 μM) evoked calcium responses in ∼50% of glia. These were suramin and PPADS sensitive and essentially abolished in SCG glial cells cultured from adult P2Y(1) receptor-deficient mice. 5. UTP (EC(50)∼25 μM) and UDP (EC(50)>200 μM) evoked suramin- and pyridoxalphosphate-6-azophenyl-2′,5′-disulphonate-sensitive rises in calcium in ∼60 and 20% SCG glial cells, respectively. 6. These results indicate the presence of several P2Y receptors coupled to an increase in intracellular calcium in the SCG: ADP-sensitive P2Y(1) receptors and UDP-sensitive P2Y(6) receptors in SCG neurons and glial cells, a novel UTP-sensitive P2Y receptor in SCG neurons and UTP- and ATP-sensitive P2Y(2) receptors in SCG glia