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Autoradiographic evidence for two classes of mu opioid binding sites in rat brain using [125I]FK33824
R B Rothman1, A E Jacobson, K C Rice
1Laboratory of Preclinical Pharmacology, NIMH, St. Elizabeths Hospital, Washington, DC 20032.
Abstract:
Previous studies demonstrated that pretreatment of brain membranes with the irreversible mu antagonist, beta-funaltrexamine (beta-FNA), partially eliminated mu binding sites [25,35], consistent with the existence of two mu binding sites distinguished by beta-FNA. This paper tests the hypothesis that the FNA-sensitive and FNA-insensitive mu binding sites have different anatomical distributions in rat brain. Prior to autoradiographic visualization of mu binding sites, [3H]oxymorphone, [3H]D-ala2-MePhe4, Gly-ol5-enkephalin (DAGO), and [125I]D-ala2-Me-Phe4-met(o)-ol]enkephalin (FK33824) were shown to selectively label mu binding sites using slide mounted sections of molded minced rat brain. As found using membranes, beta-FNA eliminated only a portion of mu binding sites. Autoradiographic visualization of mu binding sites using the mu-selective ligand [125I]FK33824 in control and FNA-treated sections of rat brain demonstrated that the proportion of mu binding sites sensitive to beta-FNA varied across regions of the brain, particularly the dorsal thalamus, ventrobasal complex and the hypothalamus, providing anatomical data supporting the existence of two classes of mu binding sites in rat brain.
Insights
This study investigated mu binding sites in the rat brain using beta-funaltrexamine (beta-FNA). Results show distinct anatomical distributions for beta-FNA-sensitive and insensitive mu binding sites, supporting their classification into two types.
Area of Science:
- Neuroscience
- Pharmacology
- Neuroanatomy
Background:
- Previous research suggests the existence of two distinct mu opioid binding sites based on their differential sensitivity to the antagonist beta-funaltrexamine (beta-FNA).
- Understanding the anatomical distribution of these sites is crucial for elucidating their specific roles in brain function.
Purpose of the Study:
- To test the hypothesis that beta-funaltrexamine (beta-FNA)-sensitive and beta-FNA-insensitive mu binding sites exhibit different anatomical distributions within the rat brain.
- To provide anatomical evidence supporting the existence of two distinct classes of mu binding sites.
Main Methods:
- Utilized autoradiographic visualization of mu binding sites in rat brain sections.
- Employed selective mu opioid ligands, including [3H]oxymorphone, [3H]DAGO, and [125I]FK33824.
- Pretreated brain sections with the irreversible mu antagonist, beta-funaltrexamine (beta-FNA), to assess binding site sensitivity.
Main Results:
- Autoradiography confirmed that beta-funaltrexamine (beta-FNA) eliminated only a portion of mu binding sites, consistent with previous membrane studies.
- The proportion of beta-funaltrexamine (beta-FNA)-sensitive mu binding sites varied significantly across different brain regions.
- Notable regional differences in sensitivity were observed in the dorsal thalamus, ventrobasal complex, and hypothalamus.
Conclusions:
- The findings provide anatomical support for the existence of two distinct classes of mu binding sites in the rat brain.
- The differential regional distribution of beta-funaltrexamine (beta-FNA)-sensitive and insensitive sites suggests specialized functions for each class.
- This study advances the understanding of opioid receptor heterogeneity and its anatomical basis in the central nervous system.