The degradation of dynorphin A in brain tissue in vivo and in vitro

Peptides. Jul-Aug 1987;8(4):701-7. doi: 10.1016/0196-9781(87)90046-5.

Abstract

The demonstration of analgesia following in vivo administration of dynorphin A (Dyn A) has been difficult. In contrast, a number of electrophysiological and behavioral effects reported with in vivo injection of Dyn A can be produced by des-tyrosine dynorphin A (Dyn A 2-17). This suggested the extremely rapid amino terminal degradation of dynorphin A. To test this hypothesis, we examined the degradation of dynorphin A following in vivo injection into the periaqueductal gray (PAG) as well as in vitro using rat brain membranes under receptor binding conditions. In vivo, we observed the rapid amino terminal cleavage of tyrosine to yield the relatively more stable destyrosine dynorphin A. This same cleavage after tyrosine was observed in vitro. Inhibition of this aminopeptidase activity in vitro was observed by the addition of dynorphin A 2-17 or dynorphin A 7-17 but not after the addition of dynorphin A 1-13, dynorphin A 1-8, dynorphin B or alpha-neo-endorphin suggesting a specific enzyme may be responsible. The detection of the behaviorally active des-tyrosine dynorphin A following in vivo injection of dynorphin A suggests that this peptide may play an important physiological role.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid
  • Dynorphins / metabolism*
  • Enkephalin, Leucine / metabolism
  • Guinea Pigs
  • Kinetics
  • Rats
  • Tritium
  • Tyrosine / metabolism

Substances

  • Tritium
  • Tyrosine
  • Enkephalin, Leucine
  • Dynorphins