Contribution of the µ opioid receptor and enkephalin to the antinociceptive actions of endomorphin-1 analogs with unnatural amino acid modifications in the spinal cord.
Peptides
; 141: 170543, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33794284
ABSTRACT
Endomorphin analogs containing unnatural amino acids have demonstrated potent analgesic effects in our previous studies. In the present study, the differences in antinociception and the mechanisms thereof for analogs 1-3 administered intracerebroventricularly and intrathecally were explored. All analogs at different routes of administration produced potent analgesia compared to the parent peptide endomorphin-1. Multiple antagonists and antibodies were used to explore the mechanisms of action of these analogs, and it was inferred that analogs 1-3 stimulated the µ opioid receptor to induce antinociception. Moreover, the antibody data suggested that analog 2 may induce the release of immunoreactive [Leu5]-enkephaline and [Met5]-enkephaline to produce a secondary component of antinociception at the spinal level and analog 3 may stimulate the the release of immunoreactive [Met5]-enkephaline at the spinal level. Finally, analogs 2 and 3 produced no acute tolerance in the spinal cord. We hypothesize that the unique characteristics of the endomorphin analogs result from their capacities to stimulate the release of endogenous antinociceptive substances.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Medula Espinal
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Encefalinas
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Receptores Opioides mu
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Analgésicos
Limite:
Animals
Idioma:
En
Revista:
Peptides
Ano de publicação:
2021
Tipo de documento:
Article