K. Flau, A. Redmer, S. Liedtke
Dec 1, 2002
Citations
1
Influential Citations
30
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Journal
British Journal of Pharmacology
Abstract
We determined the effects of nociceptin/orphanin FQ and the NOP receptor ligands acetyl‐Arg‐Tyr‐Tyr‐Arg‐Ile‐Lys‐NH2 (Ac‐RYYRIK‐NH2) and naloxone benzoylhydrazone on transmitter release in vitro. The electrically evoked tritium overflow from guinea‐pig and mouse striatal slices and guinea‐pig retinal discs preincubated with [3H]‐dopamine was inhibited by nociceptin/orphanin FQ (pEC50 7.9, 7.6 and 8.6; Emax 30, 50 and 55%). Ac‐RYYRIK‐NH2 0.032 μM and naloxone benzoylhydrazone 5 μM antagonized the effect of nociceptin/orphanin FQ in striatal slices of the guinea‐pig (apparent pA2 9.1 and 6.8) and the mouse (apparent pA2 9.2 and 7.5) and strongly attenuated the effect of nociceptin/orphanin FQ 0.1 μM in guinea‐pig retinal discs. Ac‐RYYRIK‐NH2 0.032 μM did not affect the evoked overflow by itself whereas naloxone benzoylhydrazone 5 μM inhibited it in each tissue. The electrically evoked tritium overflow from mouse brain cortex slices preincubated with [3H]‐noradrenaline was inhibited by nociceptin/orphanin FQ (pEC50 7.9, Emax 85%), Ac‐RYYRIK‐NH2 (pEC50 8.3, Emax 47%) but not affected by naloxone benzoylhydrazone 5 μM. Ac‐RYYRIK‐NH2 and naloxone benzoylhydrazone showed apparent pA2 values of 8.6 and 6.9. In conclusion, the inhibitory effect 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‐NH2 behaves as an extremely potent NOP receptor antagonist in the striatum and retina and as a partial agonist in the cortex.