Absorption of beta-casomorphins from autoperfused lamb and piglet small intestine.
beta-Casomorphins (beta-CMs) derived from milk beta-casein may exert various opiate activities in milk-fed infants. To assess the physiological significance of beta-CMs as a source of circulating opioids in infants, we measured absorption rates of several beta-CMs under near-physiological conditions using in situ autoperfused lamb intestine. The naturally occurring beta-CMs, beta-CM-7 and beta-CM-4-amide, were absorbed readily into blood with no transfer into lymph. Uptake peaked within several minutes of the luminal infusion of peptide but then declined sharply and stopped within a further 10-15 min. The recovery in blood, intestinal contents, and tissue at the end of the 30-min experiment was less than 1% of the infused dose. The low recovery was due to rapid proteolysis based on in vitro studies that demonstrated half-lives of less than 5 min in lamb blood, luminal contents, and lymph. The synthetic dipeptidyl peptidase IV-resistant analogue beta-[D-Ala2]CM- 4-amide was stable during incubation in blood, lymph, or luminal contents and was absorbed into blood at rates that were maximal within several minutes and remained steady for the 30-min period. We conclude that although natural beta-CMs are transferred across the lamb small intestine, rapid degradation within the intestinal lumen, gut epithelium, and blood would prevent entry into the circulation under normal conditions. Val-beta-CM-7, a putative stable precursor, had similar stability and kinetics of absorption to beta-CM-7, results that exclude Val-beta-CM-7 as a stable precursor for delivery of beta-CMs to the circulation. Essentially identical results to those in lambs were obtained in 7-day-old piglets.
Department of Animal Sciences, University of Adelaide, Australia.
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Read
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Lord
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Brantl
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Koch
D000595:Amino Acid Sequence; D000818:Animals; D002364:Caseins / Q000378:metabolism*; D004723:Endorphins / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D005766:Gastrointestinal Contents / Q000032:analysis; D007106:Immune Sera; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000502:physiology*; D008196:Lymph / Q000032:analysis; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000502:physiology; D009842:Oligopeptides / Q000138:chemical synthesis; D010477:Perfusion; D012756:Sheep; D013552:Swine; D013997:Time Factors
D002364:Caseins; D004723:Endorphins; D007106:Immune Sera; D009842:Oligopeptides; C021968:beta-casomorphins