Alterations in hypothalamic μ-opiate receptor—mediated responses but not methionine enkephalin or proenkephalin messenger RNA levels in rats with acute cholestasis
✍ Scribed by Mark G. Swain
- Book ID
- 102849930
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 631 KB
- Volume
- 20
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Endogenous opioids, including methionine enkephalin, have been implicated in the control of adrenocorticotrophic hormone release by acting through mu-opiate receptors in the hypothalamus. Recently, alterations in the central opioid system have been postulated to occur in cholestasis. In addition, alterations in hypothalamic corticotropin-releasing hormone content and messenger RNA levels, as well as basal release, have been described in bile duct-resected rats, and hypothalamic methionine enkephalin is colocalized with corticotropin-releasing hormone in hypothalamic neurons. Therefore hypothalamic and pituitary methionine enkephalin content and hypothalamic proenkephalin messenger RNA levels, as well as hypothalamic mu-opiate receptor-mediated responses in uitro and in uiuo, were studied in rats with acute cholestasis caused by bile duct resection and in respective controls. Hypothalamic and pituitary methionine enkephalin levels were similar in bile ductresected, sham-resected and unoperated control rats. In addition, hypothalamic proenkephalin steady state messenger RNA levels were similar in the three groups of animals. p-Opiate receptor stimulation of hypothalamic explants in uitro with the specific p-opiate receptor agonist ligand [D-Ala2,N-Me-Phe4,G1y-ol]-Enkephalin resulted in 8.2% and 16.9% inhibition of corticotropin-releasing hormone release in sham-resected and unoperated control rats, respectively. In contrast, treatment of hypothalamic explants from bile duct-resected rats with [D-Ala2,N-Me-Phe4,Gly-011-Enkephalin resulted in a significant 22.5% increase in corticotropin-releasing hormone release. Systemic administration of the p-opiate receptor agonist morphine to rats in uiuo resulted in significantly higher incre-