Ambivalent Effects on P2X3 Receptors in Rat Sensory Neurons in the Presence of Opioid Receptor Antagonists

摘要: In cultured neurons of the dorsal root ganglia (DRGs) rats, it was found that incubation these in presence 50 nM naloxone (an opioid receptor antagonist, OR antagonist) significantly increased efficacy blocking P2X3-mediated transmembrane currents induced by application an endogenous opioid, Leu-enkephalin (LEK); above were evoked α,β-Me-ATP. Under conditions preliminary 2- to 4-min-long with naloxone, 10 LEK completely blocked P2H3 (blocking developed within 2 min). control (without incubation), respective effect observed only at much higher concentrations (1 μM). Thus, IC50 inhibitory action reduced this case from 1 nM. Naloxone high μM), when applied after development effect, exerted a dissimilar influence on amplitude P2X3 currents. For time (within 2-4 min), exceeded values; later on, returned initial value. Such ambivalent peptide (LEK) is related fact G-proteins, binding ORs, can form complexes two conformations, (Gi/o) and stimulating (Gq/s). It known increase analgesic morphine due direct competitive antagonism Gq/s-bound conformation. effects opioids receptors are explained antagonist-induced shift equilibrium between conformations G-protein complexes.