title: Direct and indirect inhibition by nociceptin/orphanin FQ on noradrenaline release from rodent cerebral cortex in vitro.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, Italy. snn@ifeuniv.unife.it
authors.forename: Anna
authors.initials: A
authors.lastname: Siniscalchi
authors.forename: Donata
authors.initials: D
authors.lastname: Rodi
authors.forename: Michele
authors.initials: M
authors.lastname: Morari
authors.forename: Matteo
authors.initials: M
authors.lastname: Marti
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cavallini
authors.forename: Silvia
authors.initials: S
authors.lastname: Marino
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beani
authors.forename: Clementina
authors.initials: C
authors.lastname: Bianchi
mesh_terms: 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
chemical_list: 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