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  • Contribution of nitric oxide-dependent guanylate cyclase and reactive oxygen species signaling pathways to desensitization of μ-opioid receptors in the rat locus coeruleus.

Contribution of nitric oxide-dependent guanylate cyclase and reactive oxygen species signaling pathways to desensitization of μ-opioid receptors in the rat locus coeruleus.

Neuropharmacology (2015-08-10)
Patricia Pablos, Aitziber Mendiguren, Joseba Pineda
ABSTRACT

Nitric oxide (NO) is involved in desensitization of μ-opioid receptors (MOR). We used extracellular recordings in vitro to unmask the NO-dependent pathways involved in MOR desensitization in the rat locus coeruleus (LC). Perfusion with ME (3 and 10 μM) concentration-dependently reduced subsequent ME effect, indicative of MOR desensitization. ME (3 μM)-induced desensitization was enhanced by a NO donor (DEA/NO 100 μM), two soluble guanylate cyclase (sGC) activators (A 350619 30 μM and BAY 418543 1 μM) or a cGMP-dependent protein kinase (PKG) activator (8-pCPT-cGMP 30 μM). DEA/NO-induced enhancement was blocked by the sGC inhibitor NS 2028 (10 μM). A 350619 effect was also blocked by NS 2028, but not by the antioxidant Trolox. ME (10 μM)-induced desensitization was blocked by the neuronal NO synthase inhibitor 7-NI (100 μM) and restored by the PKG activator 8-Br-cGMP (100-300 μM). Paradoxically, ME (10 μM)-induced desensitization was not modified by sGC inhibitors (NS 2028 and ODQ), PKG inhibitors (H8 and Rp-8-Br-PET-cGMP) or antioxidant agents (Trolox, U-74389G and melatonin), but it was attenuated by a combination of NS 2028 and Trolox. In conclusion, MOR desensitization in the LC may be mediated or regulated by NO through sGC and reactive oxygen species signaling pathways.

MATERIALS
Product Number
Brand
Product Description

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