The potency of μ-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17β-estradiol

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Abstract

The μ-opioid agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol) hyperpolarizes the majority of arcuate hypothalamic (ARC) neurons by opening an inwardly rectifying potassium conductance. The EC50 for the DAMGO-induced hyperpolarization was 60 ± 3 nM in ARC neurons from ovariectomized guinea pigs. Superfusion of 17β-estradiol (E2; 100 nM) for 20 min in vitro resulted in a significant decrease in DAMGO potency (EC50 = 212 ± 16 nM) in 40% of the neurons that were tested. This rapid effect of E2 on the μ- opioid response was not mimicked by the biologically inactive isomer 17α- estradiol. Multiple concentrations of E2 were used to generate an E2 concentration-response curve, with an EC50 of 9 nM and a maximal increase in the DAMGO EC50 of 411% of controls. The membrane properties and firing rate of E2-sensitive and E2-insensitive neurons were not different. Streptavidin-FITC labeling did not reveal any significant morphological differences between the groups, but a higher number of E2-sensitive cells was found in the lateral ARC and cell-poor zone. Moreover, immunocytochemical staining of the recorded cells revealed that β-endorphin neurons were among those sensitive to E2. Therefore, E2 could increase β-endorphin release by decreasing the potency of β-endorphinergic autoinhibition, thus increasing the tonic opioid inhibition of E2-insensitive cells. Furthermore, the diffuse projections of hypothalamic β-endorphin neurons would allow E2 to alter processes throughout the brain, as well as having local effects in the hypothalamus.

Original languageEnglish (US)
Pages (from-to)6196-6204
Number of pages9
JournalJournal of Neuroscience
Volume14
Issue number10
DOIs
StatePublished - Oct 1994

Keywords

  • G-protein coupling
  • K channel
  • arcuate nucleus
  • hypothalamus
  • immunocytochemistry
  • μ-opioid receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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