caa a22 4500 606162801 CHVBK 20210128100640.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11062-015-9519-9 doi (NATIONALLICENCE)springer-10.1007/s11062-015-9519-9 Ambivalent Effects on P2X3 Receptors in Rat Sensory Neurons in the Presence of Opioid Receptor Antagonists [Elektronische Daten] [V. Kulyk, I. Chyzhmakov, T. Volkova, O. Kryshtal] In cultured neurons of the dorsal root ganglia (DRGs) of rats, it was found that incubation of these neurons in the presence of 50 nM naloxone (an opioid receptor antagonist, OR antagonist) significantly increased the efficacy of blocking of P2X3-mediated transmembrane currents induced by application of an endogenous opioid, Leu-enkephalin (LEK); the above currents were evoked by application of α,β-Me-ATP. Under conditions of preliminary 2- to 4-min-long incubation of neurons with naloxone, 10 nM LEK completely blocked P2H3 currents (blocking developed within 2 min). Under control conditions (without incubation), the respective effect was observed only at much higher LEK concentrations (1 μM). Thus, the IC50 of inhibitory LEK action was reduced in this case from 10 nM to 1 nM. Naloxone in high concentrations (1 μM), when applied after the development of the LEK inhibitory effect, exerted a dissimilar influence on the amplitude of P2X3 currents. For a time (within 2-4 min), this amplitude exceeded the control values; later on, it returned to the initial value. Such ambivalent effect of the opioid peptide (LEK) is related to the fact that G-proteins, when binding to the ORs, can form complexes in two conformations, inhibitory (Gi/o) and stimulating (Gq/s). It is known that naloxone can increase the analgesic effect of morphine due to direct competitive antagonism with the Gq/s-bound conformation. Thus, ambivalent effects of opioids on P2X3 receptors are explained by an antagonist-induced shift of the equilibrium between conformations of G-protein complexes. Springer Science+Business Media New York, 2015 primary sensory neurons nationallicence opioid receptors nationallicence P2X3 receptors nationallicence Leu-enkephalin (LEK) nationallicence naloxone nationallicence Gi/o and Gq/s proteins nationallicence Kulyk V. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut Chyzhmakov I. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut Volkova T. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut Kryshtal O. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut Neurophysiology Springer US; http://www.springer-ny.com 47/3(2015-06-01), 185-190 0090-2977 47:3<185 2015 47 11062 https://doi.org/10.1007/s11062-015-9519-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11062-015-9519-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kulyk V. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut NATIONALLICENCE 700 1- Chyzhmakov I. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut NATIONALLICENCE 700 1- Volkova T. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut NATIONALLICENCE 700 1- Kryshtal O. Bogomolets Institute of Physiology (NAS of Ukraine), Kyiv, Ukraine aut NATIONALLICENCE 773 0- Neurophysiology Springer US; http://www.springer-ny.com 47/3(2015-06-01), 185-190 0090-2977 47:3<185 2015 47 11062