IMMUNOLOCALIZATION OF 2 MU-OPIOID RECEPTOR ISOFORMS (MOR1 AND MOR1B) IN THE RAT CENTRAL-NERVOUS-SYSTEM

We have recently shown that the cytoplasmic tail of the rat mu-opioid receptor undergoes alternative splicing giving rise to two isoforms, r MOR1 and rMOR1B. These isoforms exhibit similar pharmacological profil es, however, differ in agonist-induced desensitization of coupling to adenylate cyclase. In the present study, we have raised polyclonal ant ibodies that specifically detect either rMOR1 or rMOR1B and used these antisera for immunocytochemical localization of the receptor proteins in the rat central nervous system. Prominent MOR1B-like immunoreactiv ity was found in the external plexiform layer of the main olfactory bu lb localized to a dense plexus of dendrites mostly originating from mi tral cells and extending into the glomerular layer. MOR1-like immunore activity was restricted to the perikarya of mitral cells and to distin ct juxtaglomerular cells as well as their processes. While MOR1-, DOR1 - and KOR1-like immunoreactivity was absent from the external plexifor m layer, high densities of opioid peptides were found in this layer su ggesting that MOR1B may be a targeted receptor of these peptides. MOR1 -like immunoreactivity was observed in many pain-controlling brain are as including the spinal cord dorsal horn, sensory trigeminal complex, raphe nuclei and periaqueductal gray while MOR1B-like immunoreactivity was not detectable in these regions. Taken together, we provide evide nce that the mu receptor isoforms, MOR1 and MOR1B, exhibit a strikingl y different distribution in that MOR1 appears to be the major isoform widely distributed throughout the central nervous system and MOR1B bei ng predominantly localized to the olfactory bulb. (C) 1997 IBRO. Publi shed by Elsevier Science Ltd.