A C-terminal cyclic 8-13 neurotensin fragment analog appears less exposed to neprilysin when it crosses the blood-brain barrier than the cerebrospinal fluid-brain barrier in mice

Neurosci Lett. 1996 Oct 11;217(1):58-60. doi: 10.1016/0304-3940(96)13074-3.

Abstract

A C-terminal cyclic 8-13 neurotensin fragment analog. JMV 1193, a direct agonist of central neurotensin receptors, is able to cross both the cerebrospinal fluid-brain barrier and the blood-brain barrier. When administered intracerebroventricularly (i.c.v.), its hypothermic effect was potentiated by the enkephalinase inhibition induced either by thiorphan (simultaneous intracerebroventricular administration of 10 micrograms) or by the thiorphan prodrug. acetorphan (intravenous (i.v.) administration of 10 mg/kg). Such a potentiation was not observed when both JMV 1193 and acetorphan were administered intravenously. Therefore it appears that the sensitivity of JMV 1193 to enkephalinase depends on its route of administration. It is exposed to this peptidase after i.c.v. injection (when crossing the cerebrospinal fluid-brain barrier), while it is not after i.v. administration (when crossing the blood-brain barrier).

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiology*
  • Body Temperature Regulation / physiology*
  • Brain / physiology*
  • Cerebrospinal Fluid / physiology*
  • Injections, Intravenous
  • Injections, Intraventricular
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neprilysin / antagonists & inhibitors
  • Neprilysin / pharmacology*
  • Neurotensin / analogs & derivatives*
  • Neurotensin / pharmacology
  • Peptide Fragments / pharmacology*
  • Prodrugs / pharmacology
  • Protease Inhibitors / pharmacology
  • Receptors, Neurotensin / agonists*
  • Thiorphan / analogs & derivatives
  • Thiorphan / pharmacology

Substances

  • JMV 1193
  • Peptide Fragments
  • Prodrugs
  • Protease Inhibitors
  • Receptors, Neurotensin
  • Neurotensin
  • racecadotril
  • Thiorphan
  • Neprilysin