R Alan North

..Other agonists, antagonists, and ions that can be used to differentiate among the receptors are discussed...

..In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways...

..This has been substantiated by the development by Abbott of a small molecule that selectively blocks P2X3 subunit-containing P2X receptors, and which is effective in a range of animal models of neuropathic and chronic inflammatory pain...

..The availability of such tools and experimental approaches promises to accelerate our understanding of the other physiological roles for P2X receptors on primary afferent neurones...

..Together, the clear differential effects of extracellular sodium ions or of mutation of the receptor strongly suggest that N-methyl-d-glucamine and YO-PRO-1 do not enter the cell by the same permeation pathway...

..The results suggest a "head-to-tail" subunit arrangement in the quaternary structure of P2X receptors and show that a trimeric P2X2/3 receptor would have the composition P2X2(P2X3)2...

..The findings indicate that the P2X4 receptor subunit has a very extensive distribution among mammalian tissues, and this suggests possible new functional roles...

..Cells expressing human P2X5 receptors also rapidly accumulated the propidium dye YO-PRO-1 in response to ATP...

..It reversed the rapid current deactivation at F44C/L338C. 5 The results suggest that a methanethiosulfonate binding to L338C prevents binding to F44C; this might indicate proximity of these two residues...

..Either the P2X7 protein in the hippocampus is below the limits of detection by the currently available methods or it is not present...

..The P2Y receptors are most likely P2Y1 and P2Y2 and these couple through phospholipase C to an increase in intracellular calcium and the opening of SK type potassium channels...

..that the heteromeric P2X2/3 receptor is much more tolerant of alphabeta and betagamma substitution; and (c). that a P2X2/3-selective antagonist can be obtained by introduction of additional negativity at the betagamma-methylene...

..This finding suggests that these drugs should be used with care to discriminate between P2X and neuronal acetylcholine receptor types...

..These findings suggest that the P2X(7) C-terminal domain associates with EMPs, and this interaction may mediate some aspects of the downstream signaling following P2X(7) receptor activation...

..Under these experimental conditions Kv1.3 sets the resting potential of the cells, but it is not required for Fc receptor-mediated phagocytosis...

..The results suggest that prolonged depolarization leads to an increased intracellular level of ADP-ribose, which in turn activates this nonselective conductance(s)...

..PPADS (K(D) approximately 0.1 microM) associated and dissociated some 100 - 10,000 times more slowly than the other antagonists...

..We concluded that spontaneous currents represent activation of acid-sensitive ion channels (ASICs) by autocrine vesicular release of protons from HEK cells...

..P2X receptors have a molecular architecture distinct from other ion channel protein families, and have several unique functional properties...

..Cell swelling in these mutant cells was accompanied by a marked inhibition of contractile vacuole emptying. These findings demonstrate a new functional role for P2X receptors on intracellular organelles, in this case in osmoregulation...

..The correction of this gating defect, in the absence of any agonist, by the second mutation K308A shows that Lys308 is also involved in channel gating. A similar interpretation can account for the results with suramin and TNP-ATP...

..The results indicate that the ability of ATP to gate cation permeation across membranes exists in cells that diverged in evolutionary terms from animals about 1 billion years ago...

..These residues lie between previously identified motifs involved in membrane trafficking (YXXXK and YXXGL) and implicates the C-terminal also in rearrangements leading to channel closing during the presence of agonist...

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..Furthermore, the packets of ATP appear to be released from vesicle in a subset of glutamate-containing terminals...

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..We suggest that calcium entry through subsynaptic P2X4 receptors during high-frequency stimulation contributes to synaptic strengthening...

..The failure to rescue function in the P2X2 subunit with both lysines mutated by wild-type P2X3 suggests that these residues from two different subunits interact in agonist binding or channel opening...

..In addition, ATP can be released from astroglial cells, thereby acting as a mediator of glial-glial and glial-neuronal signaling...

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..We conclude that cortical astrocytes express functional NMDA receptors that are devoid of Mg2+ block, and these receptors are involved in neuronal-glial signal transmission...

..1 nm, which closely matches FRET data. Thus, our data provide the first views of the architecture, shape, and size of single P2X receptors, furthering our understanding of this important family of ligand-gated ion channels...