Ganglion-Specific Sensitivity of P2X3 Receptors to Leu-Enkephalin
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Neurophysiology, Vol. 52, No. 3, May, 2020
Ganglion-Specific Sensitivity of P2X3 Receptors to Leu-Enkephalin V. B. Kulyk,1,2 I. V. Chizhmakov,1 O. V. Iegorova,1 T. M. Volkova,1 G. I. Kharytonenko,2 O. O. Drozd,3 and O. A. Krishtal1 Received January 12, 2020 In this study, several properties of modulation of P2X3 currents by an endogenous opioid, leu-enkephalin (LEK), in neurons of the dorsal root and nodose ganglia (DRGs and NGs, respectively) were compared. P2X3-mediated currents were recorded using a patch-clamp technique in the whole-cell configuration. P2X3 receptors in DRG neurons were found to be more sensitive to LEK application compared to NG neurons; complete suppression of the corresponding currents required lower concentrations of LEK and rose more quickly. Short-term preapplication of naloxone (a nonselective opioid receptor antagonist) on NG neurons did not alter the effect of the tested opioid on P2X3 currents, while it dramatically enhanced LEK-induced inhibition in DRG neurons. This fact may be indicative of the existence of specific intracellular pathways involved in opioid-induced modulation of P2X3 receptors of different peripheral ganglia in vertebrates.
Keywords: opioid receptors, P2X3 receptors, leu-enkephalin, naloxone, dorsal root ganglion, nodose ganglion
INTRODUCTION ATP is the main mediator in intracellular energy metabolism. Simultaneously, this substance is released in many tissues (lungs, intestines, muscles, skin, etc.) after strong mechanical deformation and at the actions of hypoxia, ischemia, and/or other damaging factors [1–3]. Extracellular ATP of this genesis can be detected by purinergic receptors in a number of the cells, in particular by ionotropic P2X and metabotropic P2Y receptors [4, 5]. The P2X receptors are involved in the control of visceral and somatic functions, in particular in the transduction of nociceptive signals [2, 3]. Heteromeric P2X2/3 and monomeric P2X3 receptors are expressed in primary afferent neurons of the dorsal root ganglia (DRGs) and nodose ganglia (NGs) [1, 6]. The P2X3mediated rapidly desensitizing currents are more typical of DRG neurons. In contrast, ATP application to a vast majority of the NG neurons initiates slow desensitizing P2X2/3- and P2X2-mediated currents; only about 10% of these cells generate P2X3mediated currents [7]. Bogomolets Institute of Physiology, NAS of Ukraine, Kyiv, Ukraine; Kyiv National University of Technologies and Design, Kyiv, Ukraine; 3 Bogomolets National Medical University, Ministry of Public Health of Ukraine, Kyiv, Ukraine. Correspondence should be addressed to V. B. Kulyk (e-mail: [email protected]). 1 2
Metabotropic receptors can modulate the acti vity of a large number of ionotropic receptors coexpressed in neurons. For instance, P2X3 currents in DRG neurons are controlled by several G-proteincoupled receptors. It is known that the activity of P2X3-receptors can be inhibited by activation of P2Y- and some opioid receptors and enhanced by activation of protease-activated receptors and also receptors to pro
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