Inhibition of striatal and retinal dopamine release via nociceptin/orphanin FQ receptors

Abstract

1 We determined the eects of nociceptin/orphanin FQ and the NOP receptor ligands acetyl-ArgTyr-Tyr-Arg-Ile-Lys-NH 2 (Ac-RYYRIK-NH 2 ) and naloxone benzoylhydrazone on transmitter release in vitro. 2 The electrically evoked tritium over¯ow from guinea-pig and mouse striatal slices and guinea-pig retinal discs preincubated with [ 3 H]-dopamine was inhibited by nociceptin/orphanin FQ (pEC 50 7.9, 7.6 and 8.6; E max 30, 50 and 55%). Ac-RYYRIK-NH 2 0.032 mM and naloxone benzoylhydrazone 5 mM antagonized the eect of nociceptin/orphanin FQ in striatal slices of the guinea-pig (apparent pA 2 9.1 and 6.8) and the mouse (apparent pA 2 9.2 and 7.5) and strongly attenuated the eect of nociceptin/orphanin FQ 0.1 mM in guinea-pig retinal discs. Ac-RYYRIK-NH 2 0.032 mM did not aect the evoked over¯ow by itself whereas naloxone benzoylhydrazone 5 mM inhibited it in each tissue. 3 The electrically evoked tritium over¯ow from mouse brain cortex slices preincubated with [ 3 H]-noradrenaline was inhibited by nociceptin/orphanin FQ (pEC 50 7.9, E max 85%), Ac-RYYRIK-NH 2 (pEC 50 8.3, E max 47%) but not aected by naloxone benzoylhydrazone 5 mM. Ac-RYYRIK-NH 2 and naloxone benzoylhydrazone showed apparent pA 2 values of 8.6 and 6.9. 4 In conclusion, the inhibitory eect of nociceptin/orphanin FQ on dopamine release in the striatum and retina and on noradrenaline release in the cerebral cortex is mediated via NOP receptors. Ac-RYYRIK-NH 2 behaves as an extremely potent NOP receptor antagonist in the striatum and retina and as a partial agonist in the cortex.

Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease

“…In fact, DA neurons projecting from substantia nigra compacta (SNc) and ventral-tegmental area to the strifatum and prefrontal cortex express the NOP receptor (Maidment et al, 2002; Norton et al, 2002). Activation of somato-dendritic NOP receptors causes inhibition of the firing activity along the nigro-striatal (Marti et al, 2004b) and meso-accumbal (Murphy and Maidment, 1999) pathways, while activation of presynaptic NOP receptors causes inhibition of DA neurosecretion (Flau et al, 2002). These effects have been associated with hypolocomotion (Murphy, 2010; Narayanan et al, 2004; Sakoori and Murphy, 2004; Viaro et al, 2013).…”

Nociceptin Inhibits Uterine Contractions in Term-Pregnant Rats by Signaling Through Multiple Pathways1

“…However, the peripheral actions of PNOC have not been fully described. Outside the brain, OPRL1 has been detected in the rat peripheral ganglia, airways, and intestines; the mice heart, vas deferens, and colon; the guinea pig retina; and in the human airways and mononuclear cells [6][7][8][9][10][11]. As regards the visceral smooth muscles, PNOC has been found to inhibit nonadrenergic-noncholinergic bronchoconstriction in the guinea pig airways via the prejunctional modulation of tachykinin release [12] and to inhibit distal colon motility in the rat [13].…”

Blockade of Nociceptin/Orphanin FQ Receptor Signaling in Rat Substantia Nigra Pars Reticulata Stimulates Nigrostriatal Dopaminergic Transmission and Motor Behavior

“…However, N/OFQ may also inhibit the nigrostriatal DAergic pathway because it reduced striatal 3 H-DA release in vitro (Flau et al, 2002), striatal DOPAC content in vivo (Shieh and Pan, 1998), and, when perfused into the substantia nigra (SN) pars reticulata (SNr), facilitated glutamate release via D 2 receptor-mediated mechanisms (Marti et al, 2002a). It is known that the opioid system regulates motor activity, at least partly, via the nigrostriatal pathway: and ␦ receptor agonists stimulate locomotion and the nigrostriatal transmission, whereas receptor agonists inhibit both (Mansour et al, 1995).…”