Anatomical and functional correlation of the endomorphins with mu opioid receptor splice variants

The present study characterizes the relationship between the endogenous mu opioid peptides endomorphin‐1 (EM‐1) and endomorphin‐2 (EM‐2) and several splice variants of the cloned mu opioid receptor (MOR‐1) encoded by the mu opioid receptor gene (Oprm). Confocal laser microscopy revealed that fibers...

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Bibliographic Details
Published in:The European journal of neuroscience 2002-09, Vol.16 (6), p.1075-1082
Main Authors: Abbadie, C., Rossi, G. C., Orciuolo, A., Zadina, J. E., Pasternak, G. W.
Format: Article
Language:English
Subjects:
alternative splicing
Alternative Splicing - genetics
Amino Acid Sequence - genetics
analgesia
Animals
antisense
Base Sequence - genetics
Exons - genetics
Immunohistochemistry
Male
Mice
Mice, Inbred Strains
MOP1
MOR-1
MOR-1C
Oligopeptides - genetics
Oligopeptides - metabolism
Oligopeptides - pharmacology
Oprm
Pain - drug therapy
Pain - metabolism
Pain - physiopathology
Posterior Horn Cells - cytology
Posterior Horn Cells - drug effects
Posterior Horn Cells - metabolism
Protein Structure, Tertiary - genetics
Receptors, Opioid, mu - drug effects
Receptors, Opioid, mu - genetics
Receptors, Opioid, mu - metabolism
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Summary:The present study characterizes the relationship between the endogenous mu opioid peptides endomorphin‐1 (EM‐1) and endomorphin‐2 (EM‐2) and several splice variants of the cloned mu opioid receptor (MOR‐1) encoded by the mu opioid receptor gene (Oprm). Confocal laser microscopy revealed that fibers containing EM‐2‐like immunoreactivity (‐LI) were distributed in close apposition to fibers showing MOR‐1‐LI (exon 4‐LI) and to MOR‐1C‐LI (exons 7/8/9‐LI) in the superficial laminae of the lumbar spinal cord. We also observed colocalization of EM‐2‐LI and MOR‐1‐LI in a few fibers of lamina II, and colocalization of EM‐2‐LI and MOR‐1C‐LI in laminae I–II, and V–VI. To assess the functional relevance of the MOR‐1 variants in endomorphin analgesia, we examined the effects of antisense treatments that targeted individual exons within the Oprm1 gene on EM‐1 and EM‐2 analgesia in the tail flick test. This antisense mapping study implied mu opioid receptor mechanisms for the endomorphins are distinct from those of morphine or morphine‐6β‐glucuronide (M6G).
ISSN:0953-816X
1460-9568
DOI:10.1046/j.1460-9568.2002.02173.x