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Title: Contribution of the intracellular C terminal domain to regulation of human P2X1 receptors for ATP by phorbol ester and Gq coupled mGlu(1α) receptors.
Authors: Wen, H
Evans, RJ
First Published: 21-Dec-2010
Publisher: Elsevier
Citation: European Journal of Pharmacology , 2011, 654 (2), pp. 155-159
Abstract: P2X1 receptors are expressed in arteries and blood platelets, play an important role in the cardiovascular system, and their activity can be potentiated following stimulation of Gq coupled receptors or phorbol ester treatment. The contribution of the intracellular carboxy terminus of the P2X1 receptor to this regulation was determined using over-expression of the C terminus and a mutagenesis based approach on recombinant receptors expressed in Xenopus oocytes. PMA induced potentiation of P2X1 receptor currents (~125% above control) was abolished following over-expression of the intracellular carboxy terminus of the P2X1 receptor. To determine the molecular basis of regulation by the carboxy terminus a series of individual cysteine point mutations between His(355) and Tyr(370) was characterized. PMA potentiation was abolished for the P2X1 receptor mutants H355C, P358C, Y363C, K367C, F368C, K369C and Y370C. When these mutations were introduced into the carboxy terminus fragment the inhibitory effect was absent only for P358C, K367C and Y370C mutants. These results suggest that residues Pro(358), Lys(367) and Tyr(370) are involved in the sequestering effect of the carboxy terminal fragment and indicate they are directly involved in modulation of the receptor by binding to a regulatory factor. The other mutants that abolished the PMA effect when introduced into the P2X1 receptor are likely to be involved in transduction of the regulatory event. These studies highlight the importance of the carboxy terminus in determining the properties and regulation of the P2X1 receptor and suggest that the intracellular terminal regions of the receptor close to the transmembrane segments interact.
DOI Link: 10.1016/j.ejphar.2010.11.039
eISSN: 1879-0712
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2010 Elsevier B.V. Under a Creative Commons license ( )
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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