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

• Published in: Neuroscience letters 1996-10, Vol.217 (1), p.58-60
• Main Authors: Van Kemmel, F.-M., Dubuc, I., Bourdel, E., Fehrentz, J.-A., Martinez, J., Costentin, J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood-brain barrier; Blood-Brain Barrier - physiology; Body Temperature Regulation - physiology; Brain - physiology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrospinal Fluid - physiology; Cerebrospinal fluid-brain barrier; Chemical Sciences; Cyclic neurotensin 8–13 fragment; Fundamental and applied biological sciences. Psychology; Injections, Intravenous; Injections, Intraventricular; JMV 1193; Male; Mice; Mice, Inbred Strains; Neprilysin (enkephalinase, EC 3.4.24-11); Neprilysin - antagonists & inhibitors; Neprilysin - pharmacology; Neurotensin - analogs & derivatives; Neurotensin - pharmacology; Organic chemistry; Peptide Fragments - pharmacology; Prodrugs - pharmacology; Protease Inhibitors - pharmacology; Receptors, Neurotensin - agonists; Thiorphan - analogs & derivatives; Thiorphan - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/0304-3940(96)13074-3

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 μg) 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).