title: Involvement of neuronal nitric oxide synthase in desensitisation of µ-opioid receptors in the rat locus coeruleus.
abstract: Nitric oxide (NO) has been recently shown to enhance µ-opioid receptor (MOR) desensitisation in locus coeruleus (LC) neurons. The aim of this study was to evaluate by single-unit extracellular recordings in rat brain slices whether the neuronal NO synthase is involved in MOR desensitisation in LC neurons. As expected, a high concentration of the opioid agonist Met(5)-enkephalin (ME; 10 µM, 10 min) strongly desensitised the inhibition induced by a test application of ME (0.8 µM, 1 min), whereas lower ME concentrations (1 and 3 µM) only weakly desensitised it. The neuronal NO synthase inhibitors 7-nitroindazole (10-100 µM), S-methyl-L-thiocitrulline (0.01-10 µM) and N(ω)-propyl-L-arginine (1-10 µM) attenuated ME (10 µM)-induced opioid desensitisation, although the endothelial NO synthase inhibitor N(5)-(1-iminoethyl)-L-ornithine (3-30 µM) failed to change it. The NO donor sodium nitroprusside (1 mM), but not its inactive analog potassium ferricyanide (1 mM), enhanced the ME (3 µM)-induced desensitisation and prevented the effect of S-methyl-L-thiocitrulline (10 µM). Sodium nitroprusside (1 mM) failed to change the desensitisation of α2-adrenoceptors by noradrenaline (100 µM, 10 min). These results suggest the contribution of NO and a neuronal type of NO synthase in homologous MOR desensitisation in rat LC neurons.
authors: Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors: María T
authors: MT
authors: Santamarta
authors: Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors: Javier
authors: J
authors: Llorente
authors: Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors: Aitziber
authors: A
authors: Mendiguren
authors: Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Spain joseba.pineda@ehu.es.
authors: Joseba
authors: J
authors: Pineda
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005292:Ferricyanides / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D005292:Ferricyanides; D007191:Indazoles; C109599:N(omega)-propylarginine; D017450:Receptors, Opioid, mu; D009599:Nitroprusside; D002956:Citrulline; C065027:N(G)-iminoethylornithine; D004744:Enkephalin, Methionine; D001120:Arginine; D009952:Ornithine; D052248:Nitric Oxide Synthase Type I; D013890:Thiourea; C086717:S-methylthiocitrulline; C028033:potassium ferricyanide; C080122:7-nitroindazole; D009638:Norepinephrine
keywords: Nitric oxide; brain slices; desensitisation; electrophysiology; locus coeruleus; noradrenaline; opiates