Molecular Assays for Characterization of Alternatively Spliced Isoforms of the Mu Opioid Receptor (MOR)

Gris, Pavel; Cheng, Philip J.; Pierson, John W.; Maixner, William; Diatchenko, Luda

doi:10.1007/978-1-60327-323-7_30

Cited by 6 publications

(2 citation statements)

References 39 publications

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“…(Gris et al, 2010; Zhang et al, 2013) Similar to the eQTL patterns observed for KAT2B and CREBBP , rs9829896 was associated with OPRM1 expression in AAs ( P =0.016) but not in EAs ( P =0.12). The drug abuse protective rs9829896-C allele was associated with higher OPRM1 expression (Figure 2c).…”

Section: Resultsmentioning

confidence: 54%

KAT2Bpolymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex

et al. 2015

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Drug abuse is a common and heritable set of disorders, but the underlying genetic factors are largely unknown. We conducted genome-wide association studies of drug abuse using 7 million imputed single nucleotide polymorphisms (SNPs) and insertions/deletions in African Americans (AAs; n=3,742) and European Americans (EAs; n=6,845). Cases were drawn from the Urban Health Study of street-recruited people, who injected drugs and reported abusing opioids, cocaine, marijuana, stimulants, and/or other drugs 10 or more times in the past 30 days, and were compared to population controls. Independent replication testing was conducted in 755 AAs and 1,131 EAs from the Genetic Association Information Network. An intronic SNP (rs9829896) in the KAT2B gene was significantly associated with drug abuse in AAs (P=4.63×10−8) and independently replicated in AAs (P=0.0019). The rs9829896-C allele (frequency=12%) had odds ratios of 0.68 and 0.53 across the AA cohorts: meta-analysis P=3.93×10−10. Rs9829896-C was not associated with drug abuse across the EA cohorts: frequency=36% and meta-analysis P=0.12. Using dorsolateral prefrontal cortex data from the BrainCloud cohort, we found that rs9829896-C was associated with reduced KAT2B expression in AAs (n=113, P=0.050) but not EAs (n=110, P=0.39). KAT2B encodes a transcriptional regulator in the cyclic adenosine monophosphate and dopamine signaling pathways, and rs9829896-C was associated with expression of genes in these pathways: reduced CREBBP expression (P=0.011) and increased OPRM1 expression (P=0.016), both in AAs only. Our study identified the KAT2B SNP rs9829896 as having novel and biologically plausible associations with drug abuse and gene expression in AAs but not EAs, suggesting ancestry-specific effects.

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Section: Resultsmentioning

confidence: 54%

KAT2Bpolymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex

et al. 2015

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“…Forskolin is a labdane diterpene produced by the Indian coleus plant, and is commonly used in medical research to raise cAMP levels (Gris et al, 2010). Forskolin re-sensitizes cell receptors by activating adenylyl cyclase (AC) to catalyze the levels of cAMP.…”

Section: Stimulation Of Campmentioning

confidence: 99%

Effect of electromagnetic field on cyclic adenosine monophosphate (cAMP) in a human mu-opioid receptor cell model

Ross

Teli

Harrison

2015

Electromagnetic Biology and Medicine

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During the cell communication process, endogenous and exogenous signaling affect normal as well as pathological developmental conditions. Exogenous influences such as extra-low-frequency electromagnetic field (EMF) have been shown to effect pain and inflammation by modulating G-protein receptors, down-regulating cyclooxygenase-2 activity, and affecting the calcium/calmodulin/nitric oxide pathway. Investigators have reported changes in opioid receptors and second messengers, such as cyclic adenosine monophosphate (cAMP), in opiate tolerance and dependence by showing how repeated exposure to morphine decreases adenylate cyclase activity causing cAMP to return to control levels in the tolerant state, and increase above control levels during withdrawal. Resonance responses to biological systems using exogenous EMF signals suggest that frequency response characteristics of the target can determine the EMF biological response. In our past research we found significant down regulation of inflammatory markers tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NFκB) using 5 Hz EMF frequency. In this study cAMP was stimulated in Chinese Hamster Ovary (CHO) cells transfected with human mu-opioid receptors, then exposed to 5 Hz EMF, and outcomes were compared with morphine treatment. Results showed a 23% greater inhibition of cAMP-treating cells with EMF than with morphine. In order to test our results for frequency specific effects, we ran identical experiments using 13 Hz EMF, which produced results similar to controls. This study suggests the use of EMF as a complementary or alternative treatment to morphine that could both reduce pain and enhance patient quality of life without the side-effects of opiates.

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Metabolic Syndrome, Alzheimer Disease, Schizophrenia, and Depression: Role for Leptin, Melatonin, Kynurenine Pathways, and Neuropeptides

Anderson¹,

Maes²

2013

Metabolic Syndrome and Neurological Disorders

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Molecular Assays for Characterization of Alternatively Spliced Isoforms of the Mu Opioid Receptor (MOR)

Cited by 6 publications

References 39 publications

KAT2Bpolymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex

KAT2Bpolymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex

Effect of electromagnetic field on cyclic adenosine monophosphate (cAMP) in a human mu-opioid receptor cell model

Metabolic Syndrome, Alzheimer Disease, Schizophrenia, and Depression: Role for Leptin, Melatonin, Kynurenine Pathways, and Neuropeptides

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