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Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Irma Onoprishvili1, Eric J Simon

  • 1Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA.

Brain Research
|September 28, 2007
PubMed

Insights

Chronic morphine treatment up-regulates mu-opioid receptors (MOP) in cells lacking filamin A, a novel finding in cell culture. In contrast, filamin A presence leads to MOP down-regulation and desensitization.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Neuroscience

Background:

  • The human mu-opioid receptor (MOP) mediates the effects of opioid drugs.
  • Filamin A is an actin-binding protein that influences cellular signaling and receptor trafficking.
  • Understanding MOP regulation is crucial for developing effective pain management strategies.

Purpose of the Study:

  • To investigate the impact of filamin A on MOP regulation by agonists.
  • To explore the mechanisms underlying MOP up-regulation and down-regulation.
  • To determine if opioid receptor up-regulation by agonists can occur in cell culture.

Main Methods:

  • Utilized M2 melanoma cells (lacking filamin A) and A7 cells (expressing filamin A).
  • Chronic treatment with morphine and other opioid agonists (methadone, levorphanol).
  • Assessed MOP-binding sites, GTPgammaS binding, and effects of antagonists (naloxone, CTAP) and pertussis toxin.

Main Results:

  • Chronic morphine down-regulated MOP in A7 cells (with filamin A) but unexpectedly up-regulated MOP in M2 cells (without filamin A).
  • Agonists like methadone and levorphanol also induced MOP up-regulation in M2 cells.
  • MOP in A7 cells was desensitized by morphine, while MOP in M2 cells showed increased signaling and was not desensitized.

Conclusions:

  • Absence of filamin A enables agonist-induced MOP up-regulation in cell culture, a previously undocumented phenomenon.
  • Filamin A appears to play a critical role in MOP down-regulation and desensitization.
  • These findings suggest distinct cellular mechanisms govern MOP regulation depending on filamin A expression.

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