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alpha N-acetyl derivatives of beta-endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice.
- Source :
-
Life sciences [Life Sci] 1991; Vol. 48 (14), pp. 1417-27. - Publication Year :
- 1991
-
Abstract
- alpha N-acetyl human beta-endorphin-(1-31) injected icv to mice antagonized the analgesic activity of beta-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of alpha N-acetyl beta-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of alpha N-acetyl human beta-endorphin-(1-31) was partially retained by the shorter peptide alpha N-acetyl human beta-endorphin-(1-27) and to a lesser extent by beta-endorphin-(1-27), beta-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated beta-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM [125I]-Tyr27 human beta-endorphin-(1-31) specific binding, the first step (20 to 30% of the binding) was abolished with an apparent IC50 of 0.35 nM, and the rest with an IC50 of 200 nM. It is suggested that alpha N-acetyl beta-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins Gi/Go.
- Subjects :
- Acetylation
Animals
Dose-Response Relationship, Drug
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Enkephalin, Leucine-2-Alanine pharmacology
Enkephalins pharmacology
Male
Mice
Structure-Activity Relationship
Tail
Time Factors
beta-Endorphin pharmacology
Pain physiopathology
beta-Endorphin analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0024-3205
- Volume :
- 48
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 2008158
- Full Text :
- https://doi.org/10.1016/0024-3205(91)90439-i