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Chunk #17 — Discussion — Effects of A112G SNP on DAMGO-stimulated [35S]GTPγS binding have sex differences

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Brain region- and sex-specific alterations in DAMGO-stimulated [(35) S]GTPγS binding in mice with Oprm1 A112G.
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We have found that male A/A mice showed higher [3H]DAMGO binding than G/G mice in more brain regions than female A/A over G/G (Wang et al., 2012). DAMGO-stimulated [35S]GTPγS binding did not show a similar trend as [3H]DAMGO binding. There are several possible contributing factors for the discordance between DAMGO-stimulated [35S]GTPγS binding and [3H]DAMGO binding to the MOPR, as we previously discussed (Wang et al., 2012). N-linked glycosylation (Knezevic, Polasek, Gornik et al., 2009; Stanta, Saldova, Struwe et al., 2010; Huang et al., 2012), regional differences in MOPR-G protein coupling efficiency (Wang, Rasakham, Huang et al., 2011), hormonal state (Loyd, Wang, and Murphy, 2008), and epigenetic regulation [reviewed in (Jessen and Auger, 2011)] may influence sex-specific protein expression. It appears that these factors affect G/G mice, but not A/A mice, of which the underlying mechanisms remain to be investigated.