Autoradiographic evidence for two classes of mu opioid binding sites in rat brain using [125I]FK33824.
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.
Rothman
R B
RB
Laboratory of Preclinical Pharmacology, NIMH, St. Elizabeths Hospital, Washington, DC 20032.
Jacobson
A E
AE
Rice
K C
KC
Herkenham
M
M
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001923:Brain Chemistry; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010111:Oxymorphone / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000032:analysis* / Q000187:drug effects; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D007457:Iodine Radioisotopes; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; C024524:beta-funaltrexamine; D010111:Oxymorphone