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  • μ-δ opioid receptor heteromer-specific signaling in the striatum and hippocampus.

μ-δ opioid receptor heteromer-specific signaling in the striatum and hippocampus.

Biochemical and biophysical research communications (2014-07-01)
Noufissa Kabli, Theresa Fan, Brian F O'Dowd, Susan R George
ABSTRACT

The μ-δ opioid receptor heteromer activates the pertussis toxin-resistant Gαz GTP-binding protein following stimulation by the δ-agonist deltorphin-II whereas μ- and δ-receptors activate the pertussis toxin-sensitive Gαi3 protein following stimulation by μ- and δ-agonists, respectively. Although the regulation of the μ-δ heteromer is being investigated extensively in vitro, its physiological relevance remains elusive owing to a lack of available molecular tools. We investigated μ-δ heteromer signaling under basal conditions and following prolonged morphine treatment in rodent brain regions highly co-expressing μ- and δ-receptors and Gαz. Deltorphin-II induced Gαz activation in the striatum and hippocampus, demonstrating the presence of μ-δ heteromer signaling in these brain regions. Prolonged morphine treatment, which desensitizes μ- and δ-receptor function, had no effect on μ-δ heteromer signaling in the brain. Our data demonstrate that μ-δ heteromer signaling does not desensitize and is regulated differently from μ- and δ-receptor signaling following prolonged morphine treatment.

MATERIALS
Product Number
Brand
Product Description

Supelco
Morphine solution, 100 μg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Morphine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Morphine sulfate salt pentahydrate