ABSTRACT
In adult humans, after milk or yogurt ingestion, many peptides derived from alpha s1-, beta- or kappa-caseins were detected in stomach, including the kappa-caseinoglycopeptide, an inhibitor of platelet aggregation. Smaller peptides derived from casein and lactoferrin were recovered from duodenum. Two long peptides, the kappa-caseinoglycopeptide and the N-terminal peptide of alpha s1-casein, were absorbed and detected in plasma. These results support the concept that food-born peptides could have physiological activities in man.
Subject(s)
Caseins/blood , Caseins/metabolism , Fibrinolytic Agents/blood , Glycopeptides/blood , Milk/metabolism , Peptide Fragments/blood , Yogurt , Adult , Amino Acid Sequence , Animals , Caseins/pharmacology , Cattle , Chromatography, High Pressure Liquid , Digestion , Duodenum/metabolism , Female , Fibrinolytic Agents/pharmacology , Gastric Mucosa/metabolism , Glycopeptides/pharmacology , Humans , Male , Middle Aged , Molecular Sequence Data , Peptide Fragments/pharmacology , Peptides/blood , Platelet AggregationABSTRACT
Several peptide inhibitors of thrombin- or collagen-induced platelet aggregation and of the interaction between glycoprotein Ib and von Willebrand factor were studied by a new method--ultrasonic interferometry (Echo Cell). Inhibition of aggregate formation in a concentration-dependent manner was observed. The sensitivity of the method was 3 to 40 times higher than that of classical turbidimetry.
Subject(s)
Peptides/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Adult , Animals , Bacterial Proteins/pharmacology , Cattle , Female , Humans , Interferometry/methods , Male , Microscopy/methods , Middle Aged , Nephelometry and Turbidimetry , Oligopeptides/pharmacology , Optics and Photonics , Platelet Adhesiveness/drug effects , UltrasonicsABSTRACT
The bovine caseinoglycopeptide (residues 106-169), the C-terminal part of kappa-casein, inhibited the von Willebrand factor-dependent platelet aggregation in a dose-dependent manner. An affinity matrix made of the caseinoglycopeptide selectively bound the platelet membrane glycoprotein GPIb alpha which contains the von Willebrand factor binding site. The amino acid residues of GPIb alpha participating in the caseinoglycopeptide binding were located after residue Glu 90.
Subject(s)
Caseins/metabolism , Peptide Fragments/metabolism , Platelet Aggregation Inhibitors/metabolism , Platelet Glycoprotein GPIb-IX Complex/metabolism , Amino Acid Sequence , Animals , Binding Sites , Caseins/pharmacology , Cattle , Chromatography, Affinity , Electrophoresis, Polyacrylamide Gel , Peptide Fragments/pharmacology , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Ristocetin/pharmacology , von Willebrand Factor/antagonists & inhibitors , von Willebrand Factor/pharmacologyABSTRACT
We have adapted the ultrasonic interferometry technique (Echo-Cell), which was initially designed to study red blood cell aggregation and agglutination, to the detection of human platelet microaggregates. The experimental parameter chosen was the slope of the signal over the first 5 minutes of sedimentation. We compared our new method with the conventional aggregometry for the measurement of aggregates after thrombin-, collagen-, and epinephrine-induced platelet activation. Under these conditions we demonstrated the particular sensibility of the present method in detecting small platelet aggregates induced in the first phase of aggregation and formed by low concentrations of agonists. Furthermore, as an illustration of this method, we showed an inhibition of the formation of thrombin-induced platelet aggregates in a concentration-dependent manner by the well known antagonist arginine-glycine-aspartic acid-serine with a median inhibitory concentration of 0.4 micromol/L, which is 30 times lower than the median inhibitory concentration found by aggregometry.
Subject(s)
Blood Platelets/diagnostic imaging , Platelet Aggregation , Blood Platelets/drug effects , Collagen/pharmacology , Epinephrine/pharmacology , Humans , Interferometry , Oligopeptides/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Thrombin/pharmacology , UltrasonographyABSTRACT
Bovine and human kappa-caseinoglycopeptides, two antithrombotic peptides derived from the corresponding kappa-caseins, were detected in physiologically active concentrations in the plasma of 5-d-old newborn infants after ingestion of cow's-milk-based formula or human milk respectively. It is suggested that these two bioactive peptides are released from milk proteins during digestion.
