Inhibition of striatal and retinal dopamine release via nociceptin/orphanin FQ receptors.
1. We determined the effects of nociceptin/orphanin FQ and the NOP receptor ligands acetyl-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)) and naloxone benzoylhydrazone on transmitter release in vitro. 2. The electrically evoked tritium overflow 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 microM and naloxone benzoylhydrazone 5 microM antagonized the effect 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 effect of nociceptin/orphanin FQ 0.1 microM in guinea-pig retinal discs. Ac-RYYRIK-NH(2) 0.032 microM did not affect the evoked overflow by itself whereas naloxone benzoylhydrazone 5 microM inhibited it in each tissue. 3. The electrically evoked tritium overflow 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 affected by naloxone benzoylhydrazone 5 microM. Ac-RYYRIK-NH(2) and naloxone benzoylhydrazone showed apparent pA(2) values of 8.6 and 6.9. 4. 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-NH(2) behaves as an extremely potent NOP receptor antagonist in the striatum and retina and as a partial agonist in the cortex.
Flau
K
K
Institut für Pharmakologie und Toxikologie, Universität Bonn, Reuterstrasse 2b, 53113 Bonn, Germany.
Redmer
A
A
Liedtke
S
S
Kathmann
M
M
Schlicker
E
E
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018847:Opioid Peptides / Q000378:metabolism* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D004298:Dopamine; D018492:Dopamine Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin