Tetrapeptide Endomorphin Analogs Require Both Full Length and Truncated Splice Variants of the Mu Opioid Receptor Gene Oprm1 for Analgesia.

ABSTRACT: The mu opioid receptor gene undergoes extensive alternative splicing. Mu opioids can be divided into three classes based on the role of different groups of splice variants. Morphine and methadone require only full length seven transmembrane (7TM) variants for analgesia, whereas IBNtxA (3'-iodobenzyol-6β-naltrexamide) needs only truncated 6TM variants. A set of endomorphin analogs fall into a third group that requires both 6TM and 7TM splice variants. Unlike morphine, endomorphin 1 and 2, DAPP (Dmt,d-Ala-Phe-Phe-NH₂), and IDAPP (3'-iodo-Dmt-d-Ala-Phe-Phe-NH₂) analgesia was lost in an exon 11 knockout mouse lacking 6TM variants. Restoring 6TM variant expression in a knockout mouse lacking both 6TM and 7TM variants failed to rescue DAPP or IDAPP analgesia. However, re-es

SUBMITTER: Marrone GF 

PROVIDER: S-EPMC5177531 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature