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Psychopharmacology

, Volume 99, Issue 3, pp 357–361 | Cite as

Rotational behaviour produced by intranigral injections of bovine and human β-casomorphins in rats

  • Mario Herrera-Marschitz
  • Lars Terenius
  • Lars Grehn
  • Urban Ungerstedt
Original Investigations

Abstract

The biological activity of β-casein derived β-casomorphin peptides was evaluated by injecting bovine β-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), the homologous sequence in human β-casein (Tyr-Pro-Phe-Val-Glu) and the corresponding N-terminal tetrapeptides into the left substantia nigra of rats. Their ability to produce rotational behaviour was compared to that produced by three reference compounds, morphine, d-ala2d-leu5enkephalin and U50,488H, ligands for μ, δ and κ types of opioid receptors, respectively. The relative potencies of β-casomorphins and morphine were compared to those tested in two in vitro assays for opioid activity: (1) inhibition of the electrically induced contraction of the isolated myenteric plexus-longitudinal muscle of the guinea-pig ileum and (2) displacement of 3H-dihydromorphine binding to brain membranes. The same ranking order of potency was found in all three assays, the peptides from human β-casein being about 10-fold less potent than those from bovine β-casein. The effects of both morphine and bovine β-casomorphin-5 in producing rotational behaviour were antagonized by naloxone; however, approximately 10-fold more naloxone was required to antagonize the β-casomorphin-5 effect than that of morphine. The present data are discussed in the light of the recent observation that high concentration of β-casomorphin-like peptides are found in the cerebrospinal fluid and plasma of women with postpartum psychosis.

Key words

Postpartum psychosis Basal ganglia β-Casein Opioid receptors Rotational behaviour Rat brain 

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References

  1. Brantl V (1984) Novel opioid derived from human β-casein: human β-casomorphins. Eur J Pharmacol 106:213–214Google Scholar
  2. Brantl V, Teschemacher H, Bläsig J, Henschen A, Lottspeich F (1981) Opioid activities of β-casomorphins. Life Sci 28:1903–1909Google Scholar
  3. Brantl V, Pfeiffer A, Herz A, Henschen A, Lottspeich F (1982) Antinociceptive potencies of β-casomorphin analogs as compared to their affinities towards μ and δ opiate receptor sites in brain and periphery. Peptides 3:793–797Google Scholar
  4. Chang K-J, Cuatrecasas P, Wei ET, Chang J-K (1982) Analgesic activity of intracerebroventricular administration of morphiceptin and β-casomorphins: correlation with the morphine (μ) receptor binding affinity. Life Sci 30:1547–1551Google Scholar
  5. Ermisch A, Ruhle H-J, Neubert K, Hartrodt B, Landgraf R (1983) On the blood-brain barrier to peptides: [3H]β-casomorphin-5 uptake by eighteen brain regions in vivo. J Neurochem 41:1229–1233Google Scholar
  6. Greenberg R, Groves ML, Dower HJ (1984) Human β-casein. Amino acid sequence and identification of phosphorylation sites. J Biol Chem 259:5132–5138Google Scholar
  7. Havemann U, Kuschinsky K (1981) Further characterization of opioid receptors in the striatum mediating muscular rigidity in rats. Naunyn-Schmiedeberg's Arch Pharmacol 317:321–325Google Scholar
  8. Henschen A, Lottspeich F, Brantl V, Teschemacher H (1979) Novel opioid peptides derived from casin (β-casomorphins). II. Structure of active components from bovine casein peptone. Hoppe-Seyler's Z Physiol Chem 360:1217–1224Google Scholar
  9. Herrera-Marschitz M (1986) Neuropharmacology and functional anatomy of the basal ganglia. Karolinska Institutet-Thesis, Stockholm, pp 1–79Google Scholar
  10. Herrera-Marschitz M, Hökfelt T, Ungerstedt U, Terenius L (1983) Functional studies with the opioid peptide dynorphin: acute effects of injections into the substantia nigra reticulata of naive rats. Life Sci [Suppl I] 33:555–558Google Scholar
  11. Herrera-Marschitz M, Hökfelt T, Ungerstedt U, Terenius L, Goldstein M (1984) Effect of intranigral injections of dynorphin, dynorphin fragments and α-neoendorphin on rotational behaviour in the rat. Eur J Pharmacol 102:213–227Google Scholar
  12. Herrera-Marschitz M, Terenius L, Grehn L, Ungerstedt U (1985) Effects of casomorphin peptides in causing rotational behaviour after injections into the substantia nigra reticulata of naive rats. Acta Physiol Scand [Suppl 542] 124:182Google Scholar
  13. Kosterlitz HW, Watt AJ (1968) Kinetic parameters of narcotic agonists and antagonists, with particular reference to N-allylnoroxymorphone (naloxone). Br J Pharmacol Chemother 33:266–276Google Scholar
  14. König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Krieger, Hamburg, pp 1–162Google Scholar
  15. Lindström LH, Nyberg F, Terenius L, Bauer K, Besev G, Gunne L-M, Lyrenäs S, Willdeck-Lund G, Lindberg B (1984) CSF and plasma β-casomorphin-like opioid peptides in postpartum psychosis. Am J Psychiatry 141:1059–1066Google Scholar
  16. Paterson SJ, Robson LE, Kosterlitz HW (1983) Classification of opioid receptors. Br Med Bull 39:31–35Google Scholar
  17. Terenius L (1974) A rapid assay affinity for the narcotic receptor in rat brain: application to methadone analogues. Acta Pharmacol Toxicol 34:88–91Google Scholar
  18. Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res 24:485–493Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Mario Herrera-Marschitz
    • 1
  • Lars Terenius
    • 2
  • Lars Grehn
    • 3
  • Urban Ungerstedt
    • 1
  1. 1.Department of PharmacologyKarolinska InstitutetStockholmSweden
  2. 2.Department of PharmacologyUniversity of UppsalaUppsalaSweden
  3. 3.Department of BiochemistryUniversity of UppsalaUppsalaSweden

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