Involvement of neuronal nitric oxide synthase in desensitisation of µ-opioid receptors in the rat locus coeruleus.
J Psychopharmacol
; 28(10): 903-14, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24961237
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.
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MEDLINE
Assunto principal:
Locus Cerúleo
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Receptores Opioides mu
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Óxido Nítrico Sintase Tipo I
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article