μ opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis

μ opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling... 1 Several studies have described functional interactions between opioid and cannabinoid receptors; the underlying mechanism(s) have not been well explored. One possible mechanism is direct receptor–receptor interactions, as has been demonstrated for a number of G‐protein‐coupled receptors. 2 In order to investigate interactions between opioid and cannabinoid receptors, we epitope tagged μ, δ and κ opioid receptors with Renilla luciferase and CB1 cannabinoid or CCR5 chemokine receptors with yellow fluorescent protein and examined the extent of substrate hydrolysis induced bioluminescence resonance energy transfer (BRET) signal. 3 We find that coexpression of opioid receptors with cannabinoid receptors, but not with chemokine receptors, leads to a significant increase in the level of BRET signal, suggesting that the opioid–cannabinoid interactions are receptor specific. 4 In order to examine the implications of these interactions to signaling, we used GTPγS binding and mitogen‐activated protein kinase (MAPK) phosphorylation assays and examined the effect of receptor activation on signaling. 5 We find that the μ receptor‐mediated signaling is attenuated by the CB1 receptor agonist; this effect is reciprocal and is seen in heterologous cells and endogenous tissue expressing both receptors. 6 In order to explore the physiological consequences of this interaction, we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro‐2A cells. 7 We find that the simultaneous activation of μ opioid and CB1 cannabinoid receptors leads to a significant attenuation of the response seen upon activation of individual receptors, implicating a role for receptor–receptor interactions in modulating neuritogenesis. British Journal of Pharmacology (2006) 148, 387–395. doi:10.1038/sj.bjp.0706757 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

μ opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis

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Publisher
Wiley
Copyright
2006 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0706757
pmid
16682964
Publisher site
See Article on Publisher Site

Abstract

1 Several studies have described functional interactions between opioid and cannabinoid receptors; the underlying mechanism(s) have not been well explored. One possible mechanism is direct receptor–receptor interactions, as has been demonstrated for a number of G‐protein‐coupled receptors. 2 In order to investigate interactions between opioid and cannabinoid receptors, we epitope tagged μ, δ and κ opioid receptors with Renilla luciferase and CB1 cannabinoid or CCR5 chemokine receptors with yellow fluorescent protein and examined the extent of substrate hydrolysis induced bioluminescence resonance energy transfer (BRET) signal. 3 We find that coexpression of opioid receptors with cannabinoid receptors, but not with chemokine receptors, leads to a significant increase in the level of BRET signal, suggesting that the opioid–cannabinoid interactions are receptor specific. 4 In order to examine the implications of these interactions to signaling, we used GTPγS binding and mitogen‐activated protein kinase (MAPK) phosphorylation assays and examined the effect of receptor activation on signaling. 5 We find that the μ receptor‐mediated signaling is attenuated by the CB1 receptor agonist; this effect is reciprocal and is seen in heterologous cells and endogenous tissue expressing both receptors. 6 In order to explore the physiological consequences of this interaction, we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro‐2A cells. 7 We find that the simultaneous activation of μ opioid and CB1 cannabinoid receptors leads to a significant attenuation of the response seen upon activation of individual receptors, implicating a role for receptor–receptor interactions in modulating neuritogenesis. British Journal of Pharmacology (2006) 148, 387–395. doi:10.1038/sj.bjp.0706757

Journal

British Journal of PharmacologyWiley

Published: Jun 1, 2006

References

  • A concept for G protein activation by G protein‐coupled receptor dimers: the transducin/rhodopsin interface
    FILIPEK, FILIPEK; KRZYSKO, KRZYSKO; FOTIADIS, FOTIADIS; LIANG, LIANG; SAPERSTEIN, SAPERSTEIN; ENGEL, ENGEL; PALCZEWSKI, PALCZEWSKI
  • Oligomerization of opioid receptors
    GOMES, GOMES; FILIPOVSKA, FILIPOVSKA; JORDAN, JORDAN; DEVI, DEVI
  • Dimerization of G protein‐coupled receptors: CB1 cannabinoid receptors as an example
    WAGER‐MILLER, WAGER‐MILLER; WESTENBROEK, WESTENBROEK; MACKIE, MACKIE

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