Identification of casoxin C, an ileum-contracting peptide derived from bovine kappa-casein, as an agonist for C3a receptors.
Casoxin C (Tyr-Ile-Pro-Ile-Gln-Tyr-Val-Leu-Ser-Arg) is a bioactive peptide that was isolated from a tryptic digest of bovine kappa-casein as an anti-opioid peptide in longitudinal strips of guinea pig ileum. Casoxin C also evokes contraction of the ileal strips, and we found that this process was biphasic with rapid and slow components. The contractile profile was very similar to that of human complement C3a(70-77), which is the COOH-terminal octapeptide of C3a and has, although less potent, qualitatively the same biological activities as C3a. Casoxin C also has homology with C3a(70-77). The rapid contraction was mediated by histamine release and the slow contraction was mediated by a prostaglandin E2-like substance, judging from the effects of various pharmacological inhibitors and antagonists on the ileal contraction. Casoxin C had affinity for C3a receptors (IC50 = 40 microM) in the radioreceptor assay. In addition, casoxin C showed phagocyte-stimulating activities. Casoxin C is therefore the first milk-derived peptide identified, that acts through complement C3a receptors.
Takahashi
M
M
Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan.
Moriguchi
S
S
Suganuma
H
H
Shiota
A
A
Tani
F
F
Usui
H
H
Kurahashi
K
K
Sasaki
R
R
Yoshikawa
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002364:Caseins / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D015926:Complement C3a / Q000737:chemistry / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D011485:Protein Binding; D011738:Pyrilamine / Q000494:pharmacology; D011951:Receptors, Complement / Q000819:agonists* / Q000378:metabolism / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D002364:Caseins; D004745:Enkephalins; D008565:Membrane Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D011951:Receptors, Complement; D017450:Receptors, Opioid, mu; C106653:casoxin C; C085567:complement C3a receptor; C091249:oryzatensin; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D015926:Complement C3a; D011738:Pyrilamine; D015232:Dinoprostone