Quantitative autoradiography of [3H]CTOP binding to mu opioid receptors in rat brain

Hawkins, Kumiko N.; Knapp, Richard J.; Gehlert, Donald R.; Lui, George K.; Yamamura, Mark S.; Roeske, L; Hruby, Victor J.; Yamamura, Henry I.

doi:10.1016/0024-3205(88)90322-0

Cited by 21 publications

(3 citation statements)

References 29 publications

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“…Previous studies have also described that OR and SSTR subtypes functionally interact with each other in heterologous systems and modulate receptor pharmacology and trafficking [28]. Furthermore, SST analogues exhibit the displacement of opiate binding in rat brain membrane suggesting the ability of SST to bind and activate ORs [29]–[35]. These are compelling pieces of evidence supporting the notion that SSTR and OR subtypes might functionally interact in a native system.…”

Section: Introductionmentioning

confidence: 60%

δ-Opioid Receptor and Somatostatin Receptor-4 Heterodimerization: Possible Implications in Modulation of Pain Associated Signaling

Somvanshi

Kumar

2014

PLoS ONE

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Pain relief is the principal action of opioids. Somatostatin (SST), a growth hormone inhibitory peptide is also known to alleviate pain even in cases when opioids fail. Recent studies have shown that mice are prone to sustained pain and devoid of analgesic effect in the absence of somatostatin receptor 4 (SSTR4). In the present study, using brain slices, cultured neurons and HEK-293 cells, we showed that SSTR4 and δ-Opioid receptor (δOR) exist in a heteromeric complex and function in synergistic manner. SSTR4 and δOR co-expressed in cortical/striatal brain regions and spinal cord. Using cultured neuronal cells, we describe the heterogeneous complex formation of SSTR4 and δOR at neuronal cell body and processes. Cotransfected cells display inhibition of cAMP/PKA and co-activation of SSTR4 and δOR oppose receptor trafficking induced by individual receptor activation. Furthermore, downstream signaling pathways either associated with withdrawal or pain relief are modulated synergistically with a predominant role of SSTR4. Inhibition of cAMP/PKA and activation of ERK1/2 are the possible cellular adaptations to prevent withdrawal induced by chronic morphine use. Our results reveal direct intra-membrane interaction between SSTR4 and δOR and provide insights for the molecular mechanism for the anti-nociceptive property of SST in combination with opioids as a potential therapeutic approach to avoid undesirable withdrawal symptoms.

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Section: Introductionmentioning

confidence: 60%

δ-Opioid Receptor and Somatostatin Receptor-4 Heterodimerization: Possible Implications in Modulation of Pain Associated Signaling

Somvanshi

Kumar

2014

PLoS ONE

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“…This indicates that the EM-TAMRA bound endogenous μ-OR in keratinocytes does not respond to classical pharmacological OR antagonists as opposed to isolated membrane binding assays or animal models [ 50 , 57 ]. The physiological environment in basal and differentiated keratinocyte cultures could potentially affect the affinity of CTOP to the endogenous μ-OR since studies related to sodium ion concentration show lower affinity of CTOP [ 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating endogenous µ-opioid receptors in human keratinocytes as pharmacological targets using novel fluorescent ligand

et al. 2017

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Opioids in skin function during stress response, regeneration, ageing and, particularly in regulating sensation. In chronic pruritus, topical treatment with Naltrexone changes μ-opioid receptor (μ-OR) localization to relieve itch. The molecular mechanisms behind the effects of Naltrexone on μ-OR function in reduction of itching behavior has not been studied. There is an immediate need to understand the endogenous complexity of μ-OR dynamics in normal and pathological skin conditions. Here we evaluate real-time behavior of μ-OR-Endomorphine complexes in the presence of agonist and antagonists. The μ-OR ligand Endomorphine-1 (EM) was conjugated to the fluorescent dye Tetramethylrhodamine (TAMRA) to investigate the effects of agonist and antagonists in N/TERT-1 keratinocytes. The cellular localization of the EM-TAMRA was followed through time resolved confocal microscopy and population analysis was performed by flow cytometry. The in vitro analyses demonstrate fast internalization and trafficking of the endogenous EM-TAMRA-μ-OR interactions in a qualitative manner. Competition with Endomorphine-1, Naltrexone and CTOP show both canonical and non-canonical effects in basal and differentiated keratinocytes. Acute and chronic treatment with Naltrexone and Endomorphine-1 increases EM-TAMRA binding to skin cells. Although Naltrexone is clinically effective in relieving itch, the mechanisms behind re-distribution of μ-ORs during clinical treatments are not known. Our study has given insight into cellular mechanisms of μ-OR ligand-receptor interactions after opioid agonist and antagonist treatments in vitro. These findings potentially offer opportunities in using novel treatment strategies for skin and peripheral sensory disorders.

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“…Higher µ-receptor density has been found for the thalamus, caudate putamen, neocortex, periaqueductal gray and the dorsal horn of the spinal cord [8]. The olfactory bulb, neocortex, caudate putamen, nucleus accumbens and amygdala are rich in δ-receptors.…”

Section: The Opioid Systemmentioning

confidence: 86%

Design, synthesis and pharmacological evaluation of novel endomorphin analogues with multiple structural modifications

Mallareddy

Borics

Keresztes

et al. 2011

Pharmacological Reports

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Quantitative autoradiography of [3H]CTOP binding to mu opioid receptors in rat brain

Cited by 21 publications

References 29 publications

δ-Opioid Receptor and Somatostatin Receptor-4 Heterodimerization: Possible Implications in Modulation of Pain Associated Signaling

δ-Opioid Receptor and Somatostatin Receptor-4 Heterodimerization: Possible Implications in Modulation of Pain Associated Signaling

Investigating endogenous µ-opioid receptors in human keratinocytes as pharmacological targets using novel fluorescent ligand

Design, synthesis and pharmacological evaluation of novel endomorphin analogues with multiple structural modifications

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