The mu-opioid receptor gene polymorphism (A118G) alters HPA axis activation induced by opioid receptor blockade
| Autor: | Ahmed Ali, Joanna Reynolds, Shing Lee, Mary E. McCaul, Gary S. Wand, Deidre Gotjen, Xioaju Yang |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Hypothalamo-Hypophyseal System Protein Denaturation medicine.drug_class Narcotic Antagonists Receptors Opioid mu Nerve Tissue Proteins Biology Corticotropin-releasing hormone Estrogen-related receptor alpha Opioid receptor Internal medicine medicine Humans ACTH receptor Receptor Glucagon-like peptide 1 receptor Insulin-like growth factor 1 receptor Pharmacology Serotonin Plasma Membrane Transport Proteins Membrane Glycoproteins Polymorphism Genetic Naloxone Reverse Transcriptase Polymerase Chain Reaction Membrane Transport Proteins DNA Hormones Psychiatry and Mental health Endocrinology Amino Acid Substitution Interleukin-21 receptor Mutation Receptors Opioid Electrophoresis Polyacrylamide Gel Carrier Proteins hormones hormone substitutes and hormone antagonists Personality |
| Zdroj: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 26(1) |
| ISSN: | 0893-133X |
| Popis: | An A118G nucleotide exchange in exon 1 of the mu-opioid receptor causes an Asn40Asp substitution polymorphism in the receptor's extracellular domain. In vitro studies show that the Asp40 variant of the mu-opioid receptor binds beta-endorphin three times more avidly than the more common Asn40 variant. Paraventricular corticotropin releasing hormone neurons, which activate the HPA axis, express mu-opioid receptors and are modulated by beta-endorphin neurons. This preliminary study was designed to test the hypothesis that the Asn40Asp substitution polymorphism in the mu-opioid receptor influences HPA axis activation induced by opioid receptor blockade. Thirty-nine healthy men were genotyped (A vs. G) and then underwent opioid receptor blockade with Naloxone. Subjects expressing the A118G receptor variant had greater cortisol responses to opioid receptor blockade. Also, a significant difference in the rate of increase of ACTH (slope) between A/A and A/G was observed between 30-90 minutes as well as a significant difference in the rate of decrease after 90 minutes. Moreover, subjects expressing the variant polymorphism had lower scores on the Conscientiousness Factor and associated subscales of NEO Personality Inventory compared to subjects expressing the common receptor. Because serotonin also modulates the CRF neuron, subjects were genotyped for a functional polymorphism within the serotonin transporter gene. We did not see differences in hormone responses resulting from expression of this functional polymorphism. It is plausible that persons expressing the mu-opioid receptor variant have altered HPA axis dynamics and altered responses to other physiological processes regulated through activation of the mu-opioid receptor. |
| Databáze: | OpenAIRE |
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