Suppression by dynorphin A and [des-Tyr1]dynorphin A peptides of the expression of opiate withdrawal and tolerance in morphine-dependent mice

A. E. Takemori, Horace H Loh, N. M. Lee

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Abstract

Previously, we demonstrated that the expression of opiate withdrawal and antinociceptive tolerance can be suppressed by dynorphin (dyn) A-(1-13) in morphine-dependent mice. In this study, it was shown that the normal, endogenous dyn, dyn A-(1-17) also possessed this suppressive property. While using the nonopioid dyn analog, [des-Tyr1]dyn A [dyn A-(2-17)] as a negative control, we discovered unexpectedly that this peptide fragment also suppressed naloxone-induced withdrawal and the expression of morphine tolerance in morphine-dependent mice. Thus, an extensive structure activity relationship was studied using 11 peptide fragments. It was determined that the amino acid sequence of dyn A was required for the suppressive activity because dyn B and α-neoendorphin both failed to suppress naloxone- precipitated withdrawal jumping. Of the [des-Tyr1]dyn fragments, the minimal amino acid sequence required to suppress naloxone-induced withdrawal was determined to be dyn A-(2-8), containing the sequence G-G-F-L-R-R-I.

Original languageEnglish (US)
Pages (from-to)121-124
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume266
Issue number1
StatePublished - 1993

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