THE KAPPA-OPIOID RECEPTOR IS PRIMARILY POSTSYNAPTIC - COMBINED IMMUNOHISTOCHEMICAL LOCALIZATION OF THE RECEPTOR AND ENDOGENOUS OPIOIDS

Antisera were raised against a synthetic peptide corresponding to the carboxyl terminus of the kappa-opioid receptor (KOR1). Specificity of the antisera was verified by staining of COS-7 cells transfected with KOR1 and epitope-tagged KOR1 cDNAs, by recognition by the antisera of proteins on Western blots of both transfected cells and brain tissue, by the absence of staining of both brain tissue and transfected cells after preabsorption of the antisera with the cognate peptide, and on t he strong correlation between the distribution of KOR1 immunoreactivit y and that of earlier ligand binding and in situ hybridization studies , Results indicate that KOR1 in neurons is targeted into both the axon al and somatodendritic compartments, but the majority of immunostainin g was seen in the somatodendritic compartment, In sections from rat an d guinea pig brain, prominent KOR1 staining was seen in the ventral fo rebrain, hypothalamus, thalamus, posterior pituitary, and midbrain. Wh ile the staining pattern was similar in both species, distinct differe nces were also observed. The distribution of preprodynorphin and KOR1 immunoreactivity was complementary in many brain regions, suggesting t hat KOR1 is poised to mediate the physiological actions of dynorphin. However, the distribution of KOR1 and enkephalin immunoreactivity was complementary in some regions as well. These results suggest that the KOR1 protein is primarily, but not exclusively, deployed to postsynapt ic membranes where it mediates the effects of products of preprodynorp hin and possibly preproenkephalin.