Selective potentiation of homomeric P2X2 ionotropic ATP receptors by a fast non-genomic action of progesterone.
Neuropharmacology. 2010-03-01; 58(3): 569-577
DOI: 10.1016/j.neuropharm.2009.12.002
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1. Neuropharmacology. 2010 Mar;58(3):569-77. doi: 10.1016/j.neuropharm.2009.12.002.
Epub 2009 Dec 16.
Selective potentiation of homomeric P2X2 ionotropic ATP receptors by a fast
non-genomic action of progesterone.
De Roo M(1), Boué-Grabot E, Schlichter R.
Author information:
(1)Institut des Neurosciences Cellulaires et Intégratives, UPR 3212 Centre
National de la Recherche Scientifique, Université de Strasbourg, Département
Nociception et Douleur, 21 rue René Descartes, F-67084 Strasbourg cedex, France.
P2X receptors are ligand-gated ion channels activated by ATP that are widely
expressed in the organism and regulate many physiological functions. We have
studied the effect of progesterone (PROG) on native P2X receptors present in rat
dorsal root ganglion (DRG) neurons and on recombinant P2X receptors expressed in
HEK293 cells or Xenopus laevis oocytes. The effects of PROG were observed and
already maximal during the first coapplication with ATP and did not need any
preincubation of the cells with PROG, indicating a fast mechanism of action. In
DRG neurons, PROG rapidly and reversibly potentiated submaximal but not
saturating plateau-like currents evoked by ATP, but had no effect on the currents
activated by alpha,beta-methylene ATP, an agonist of homomeric or heteromeric
receptors containing P2X1 or P2X3 subunits. In cells expressing homomeric P2X2
receptors, responses to submaximal ATP, were systematically potentiated by PROG
in a dose-dependent manner with a threshold between 1 and 10 nM. PROG had no
effect on ATP currents carried by homomeric P2X1, P2X3, and P2X4 receptors or by
heteromeric P2X1/5 and P2X2/3 receptors. We conclude that PROG selectively
potentiates homomeric P2X2 receptors and, in contrast with dehydroepiandrosterone
(DHEA), discriminates between homomeric and heteromeric P2X2-containing
receptors. This might have important physiological implications since the P2X2
subunit is the most widely distributed P2X subunit in the organism. Moreover,
DHEA and PROG might be useful tools to clarify the distribution and the role of
native homo- and heteromeric P2X2 receptors.
Copyright 2009 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuropharm.2009.12.002
PMID: 20004677 [Indexed for MEDLINE]