Suppression by dynorphin A and [des-Tyr1]dynorphin A peptides of the expression of opiate withdrawal and tolerance in morphine-dependent mice.
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 alpha-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.
Takemori
A E
AE
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis.
Loh
H H
HH
Lee
N M
NM
D000595:Amino Acid Sequence; D000818:Animals; D004361:Drug Tolerance; D004399:Dynorphins / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000188:drug therapy / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010446:Peptide Fragments / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D010446:Peptide Fragments; C082228:dynorphin A, desTyr(1)-Gly(2)-; D009270:Naloxone; D004399:Dynorphins; D009020:Morphine; C082245:dynorphin (2-17)