Direct and indirect inhibition by nociceptin/orphanin FQ on noradrenaline release from rodent cerebral cortex in vitro.
1 The modulation exerted by nociceptin/orphanin FQ (NC) on noradrenaline (NE) release in rodent cerebral cortex slices and synaptosomes was studied. 2 Rat, mouse and guinea-pig cortical slices and synaptosomes were preincubated with 0.1 micro M [(3)H]-NE and superfused. NE release was evoked by 2 min of electrical (3 Hz) stimulation in slices and by 1 min pulse of 10 mM KCl in synaptosomes. 3 In rat cortical slices, 0.01-3 micro M NC reduced the evoked [(3)H]-NE efflux (E(max)-54%), with a bell-shaped concentration-response curve, which regained its monotonic nature in the presence of either 0.1 micro M naloxone (NX) or 30 micro M bicuculline. In synaptosomes, the NC effect curve was sygmoidal in shape and reached a plateau at 1 micro M concentration. 4 In the rat, both 1 micro M [Phe(1)psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) and 10 micro M [Nphe(1)]NC(1-13)NH(2) (NPhe) antagonised NC-induced inhibition, without per se modifying [(3)H]-NE efflux. The effects of 0.3-1 micro M NC concentrations were partially prevented by 1 micro M NX; 1 micro M D-Phe-Cys-Thr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) was also an effective antagonist, but 0.1 micro M norbinaltorphimine was not. 5 In the mouse cerebral cortex, NC-induced inhibition of NE release (pEC(50) 6.87, E(max)-61%, in the slices) was prevented by Nphe but was NX-insensitive. In guinea-pig cortical slices, NC effect (pEC(50) 6.22, E(max)-38%) was prevented by Nphe, but was NX-insensitive. 6 These findings demonstrate that NC inhibits NE release from rodent cerebral cortex via presynaptically located ORL(1) receptors. In the rat, micro opioid and GABA(A) receptors are involved as well.
Siniscalchi
Anna
A
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, Italy. snn@ifeuniv.unife.it
Rodi
Donata
D
Morari
Michele
M
Marti
Matteo
M
Cavallini
Sabrina
S
Marino
Silvia
S
Beani
Lorenzo
L
Bianchi
Clementina
C
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D004558:Electric Stimulation; D018846:Excitatory Amino Acids / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D018847:Opioid Peptides / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity; D013574:Synaptosomes / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018846:Excitatory Amino Acids; D009292:Narcotic Antagonists; D009638:Norepinephrine; D018847:Opioid Peptides; D011963:Receptors, GABA-A; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; D000097629:Nociceptin