Abstract
The endogenous opioid neurotransmitter β-endorphin (β-END), a product of the proopiomelanocortin (POMC) gene, is strongly implicated in the control of the female reproductive cycle, stress responses, and antinociception. Using selective gene targeting, we have generated a strain of mice that do not express any β-END. These mice exhibit both normal reproduction and normal basal and stress-induced hypothalamic-pituitary-axis activity, but exhibit a significantly attenuated opioid-mediated stress-induced analgesia. To further understand the cellular bases of these responses, we have studied medio-basal hypothalamic (MBH) neurons, including POMC neurons, using whole-cell patch recording in an in vitro slice preparation. Twenty-seven MBH cells were recorded in wild-type and 25 MBH cells were recorded in β-END knockout mice. Neurons from both genotypes showed a significant positive correlation between DAMGO concentration (from 30 nM to 10 μM) and the induced outward K+ current. The genotypes did not differ, however, in either the DAMGO-induced maximum outward current response or EC50, or for the maximal response to the GABA(B) agonist baclofen. Furthermore, quantitative receptor autoradiography utilizing 3H-DAMGO did not reveal any differences in total μ-opioid receptor binding between genotypes. Therefore, we conclude that the complete absence of β-END throughout development did not alter either the expression of μ-opioid receptors or their coupling to K+ channels in MBH neurons. Copyright (C) 2000 S. Karger AG, Basel.
Original language | English (US) |
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Pages (from-to) | 208-217 |
Number of pages | 10 |
Journal | Neuroendocrinology |
Volume | 72 |
Issue number | 4 |
DOIs | |
State | Published - 2000 |
Keywords
- Beta-endorphin
- Immunocytochemistry
- K channels
- Mouse
- Opioid peptide agonists
- Opioid peptides
- Proopiomelanocortin
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology
- Endocrine and Autonomic Systems
- Cellular and Molecular Neuroscience