Rotational behaviour produced by intranigral injections of bovine and human beta-casomorphins in rats.
The biological activity of beta-casein derived beta-casomorphin peptides was evaluated by injecting bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), the homologous sequence in human beta-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-leu5 enkephalin and U50,488H, ligands for mu, delta and kappa types of opioid receptors, respectively. The relative potencies of beta-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 beta-casein being about 10-fold less potent than those from bovine beta-casein. The effects of both morphine and bovine beta-casomorphin-5 in producing rotational behaviour were antagonized by naloxone; however, approximately 10-fold more naloxone was required to antagonize the beta-casomorphin-5 effect than that of morphine. The present data are discussed in the light of the recent observation that high concentrations of beta-casomorphin-like peptides are found in the cerebrospinal fluid and plasma of women with postpartum psychosis.
Herrera-Marschitz
M
M
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Terenius
L
L
Grehn
L
L
Ungerstedt
U
U
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D002417:Cattle; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007267:Injections; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra
D004723:Endorphins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C030279:enkephalinamide-Leu, Ala(2)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C021968:beta-casomorphins