Casomorphins

Definition
Casomorphins are peptides resulting from the digestion of beta-Casein and vary from 4-11 amino acids in length1. They exhibit opioid or morphine-like functions1.

Discovery
Casomorphins were first purified from casein digest of guinea pig ileum based on their ability to show opioid activity2.

Classification
Casomorphins are opioid peptides1. The most commonly studied peptides are ß-Casomorphins (BCM) which are several in number: Bovine BCM-4, Bovine BCM-5, Bovine BCM-6, Bovine BCM-7, Bovine BCM-8, Bovine BCM-11, Human BCM-7, Human BCM-81.

Structural Characteristics
BCMs are 4-11 amino acids in length. The sequences of naturally occurring BCMs are given below1:
Bovine BCM-4 Tyr-Pro-Phe-Pro,
Bovine BCM-5 Tyr-Pro-Phe-Pro-Gly
Bovine BCM-6 Tyr-Pro-Phe-Pro-Gly-Pro
Bovine BCM-7 Tyr-Pro-Phe-Pro-Gly-Pro-Ile
Bovine BCM-8 Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro
Bovine BCM-11 Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn-Ser-Leu
Human BCM-7 Tyr-Pro-Phe-Val-Glu-Pro-Ile
Human BCM-8 Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro

Mode of action
The exact mechanism of BCM function is not known. They exert their opioid functions by binding to opioid receptors on cell membranes4. Recent studies have shown that BCM-7 is an high affinity ligand for angiotensin receptor in the brain4.

Functions
BCMs produce effects in the gastrointestinal tract. For instance they influence post prandial metabolism by stimulating the secretion of insulin and somatostatin and modulate transfer of amino acids in the intestine5. The affect hypoxia as it has been shown that BCM7 when administered to pregnant rats induces their recovery from hypoxic condition4. BCM-5 and analogs are involved in producing rotational behavior in rats6. BCM-8 is involved in interplay between mother and child during lactation7. Finally, BCMs have been implicated in several diseases including SIDS and childhood autism1.

References
1.Kamiñski S, Cieoeliñska A, Kostyra E (2007). Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet, 48(3),189–198.
2.Ramabadran K, Bansinath M (1989). Pharmacology of beta-casomorphins, opioid peptides derived from milk protein. Asia Pac J Pharmacol, 4, 45–58.
3.Sobirov MM, Khalikov ShKh, Saidov SS, Kodirov MZ, Zaitsev SV, Chichenkov ON, Varfolomeev SD (1994). Synthesis and biological activity of new analogs of beta-casomorphine-5. Bioorg Khim., 20(7), 740-50.
4.Book: Handbook of Biologically Active Peptides by Abba J. Kastin.
5.Zoghbi S, Trompette A, Claustre J, Homsi ME, Garzo´n J, Jourdan G, Scoazec JY and Plaisancie P (2006). Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a opioid pathway. Am J Physiol Gastrointest Liver Physiol, 290, G1105–G1113.
6.Marschitz HM, Terenius L, Grehn L, Ungerstedt U (1989). Rotational behaviour produced by intranigral injections of bovine and human beta-casomorphins in rats. Psychopharmacology (Berl)., 99(3), 357-61.
7.Ivano DN, Richard JF, Hannu JTK, Yves LR, Chris TL, Inga T, Daniel T, Renger W, (2009). Review of the potential health impact of ß-casomorphins and related peptides. EFSA Scientific Report, 231, 1-107.