A novel insertional mutation in the mu-opioid receptor gene is associated with altered cortisol response to naloxone

Research output: Contribution to journalArticle

Abstract

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a physiological response to stress. Opioidergic pathways have a constitutionally maintained inhibitory effect on HPA activation, mediated by μ-opioid receptors expressed on corticotropin releasing factor (CRF)-expressing neurons. The opioid receptor antagonist, naloxone, activates CRF secretion by disinhibiting opioid tone and causes an increase in plasma cortisol. We have identified a subject who presented a uniquely severe adverse reaction to naloxone infusion, and a significantly blunted cortisol response to the drug. This subject carries a heterozygous mutation in the extracellular domain of the μ-opioid receptor, which causes the insertion of an extra glycine between residue 63 and 64 in the extracellular domain. Although a causal effect between the abnormality in the receptor and the unusual response to naloxone could not be proven, this insertion was not found in 300 normal chromosomes, indicating that, if it is a polymorphism, it is extremely rare.

Original languageEnglish (US)
Pages (from-to)129-133
Number of pages5
JournalJournal of Endocrine Genetics
Volume3
Issue number3-4
StatePublished - 2003

Fingerprint

mu Opioid Receptor
Naloxone
Hydrocortisone
Corticotropin-Releasing Hormone
Opioid Receptors
Mutation
Genes
Physiological Stress
Narcotic Antagonists
Glycine
Opioid Analgesics
Chromosomes
Neurons
Pharmaceutical Preparations

Keywords

  • μ-opioid receptor
  • Mutation
  • Naloxone

ASJC Scopus subject areas

  • Genetics(clinical)
  • Endocrinology
  • Genetics

Cite this

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title = "A novel insertional mutation in the mu-opioid receptor gene is associated with altered cortisol response to naloxone",
abstract = "Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a physiological response to stress. Opioidergic pathways have a constitutionally maintained inhibitory effect on HPA activation, mediated by μ-opioid receptors expressed on corticotropin releasing factor (CRF)-expressing neurons. The opioid receptor antagonist, naloxone, activates CRF secretion by disinhibiting opioid tone and causes an increase in plasma cortisol. We have identified a subject who presented a uniquely severe adverse reaction to naloxone infusion, and a significantly blunted cortisol response to the drug. This subject carries a heterozygous mutation in the extracellular domain of the μ-opioid receptor, which causes the insertion of an extra glycine between residue 63 and 64 in the extracellular domain. Although a causal effect between the abnormality in the receptor and the unusual response to naloxone could not be proven, this insertion was not found in 300 normal chromosomes, indicating that, if it is a polymorphism, it is extremely rare.",
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T1 - A novel insertional mutation in the mu-opioid receptor gene is associated with altered cortisol response to naloxone

AU - Salvatori, Roberto

AU - Yang, Xiaoju

AU - Wand, Gary S

PY - 2003

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N2 - Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a physiological response to stress. Opioidergic pathways have a constitutionally maintained inhibitory effect on HPA activation, mediated by μ-opioid receptors expressed on corticotropin releasing factor (CRF)-expressing neurons. The opioid receptor antagonist, naloxone, activates CRF secretion by disinhibiting opioid tone and causes an increase in plasma cortisol. We have identified a subject who presented a uniquely severe adverse reaction to naloxone infusion, and a significantly blunted cortisol response to the drug. This subject carries a heterozygous mutation in the extracellular domain of the μ-opioid receptor, which causes the insertion of an extra glycine between residue 63 and 64 in the extracellular domain. Although a causal effect between the abnormality in the receptor and the unusual response to naloxone could not be proven, this insertion was not found in 300 normal chromosomes, indicating that, if it is a polymorphism, it is extremely rare.

AB - Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a physiological response to stress. Opioidergic pathways have a constitutionally maintained inhibitory effect on HPA activation, mediated by μ-opioid receptors expressed on corticotropin releasing factor (CRF)-expressing neurons. The opioid receptor antagonist, naloxone, activates CRF secretion by disinhibiting opioid tone and causes an increase in plasma cortisol. We have identified a subject who presented a uniquely severe adverse reaction to naloxone infusion, and a significantly blunted cortisol response to the drug. This subject carries a heterozygous mutation in the extracellular domain of the μ-opioid receptor, which causes the insertion of an extra glycine between residue 63 and 64 in the extracellular domain. Although a causal effect between the abnormality in the receptor and the unusual response to naloxone could not be proven, this insertion was not found in 300 normal chromosomes, indicating that, if it is a polymorphism, it is extremely rare.

KW - μ-opioid receptor

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