Influence of the lactokinin Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR) on the release of endothelin-1 by endothelial cells.
Milk protein-derived peptides with angiotensin-converting enzyme (ACE) inhibitory activity can reduce blood pressure in hypertensive subjects. The lactokinin Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR) is an ACE-inhibitory peptide released by tryptic digestion from the milk protein beta-lactoglobulin. Its ACE-inhibitory activity is 100 times lower than that of captopril. The latter is known to inhibit the release of the vasoconstrictor endothelin-1 (ET-1) by endothelial cells. The effects of ALPMHIR on the endothelium are currently unknown. In this study, the influence of ALPMHIR on release of ET-1 by endothelial cells was investigated. The basal ET-1 release of the cells was reduced by 29% (p<0.01) in the presence of 1 mM ALPMHIR, compared to 42% (p<0.01) for 0.1 mM captopril. Addition of 10 U/ml thrombin to the incubation medium increased the release of ET-1 by 66% (p<0.01). Co-incubation of 10 U/ml thrombin with 1 microM captopril or with 0.1 mM ALPMHIR inhibited the stimulated ET-1 release by 45% (p<0.01) and by 32% (p<0.01), respectively. These data indicate that dietary peptides, such as ALPMHIR, can modulate ET-1 release by endothelial cells. These effects, among other mechanisms, may play a role in the anti-hypertensive effect of milk protein-derived peptides.
Maes
Wim
W
Department of Food Technology and Nutrition, Faculty of Agricultural and Applied Biological Sciences, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
Van Camp
John
J
Vermeirssen
Vanessa
V
Hemeryck
Mattias
M
Ketelslegers
Jean Marie
JM
Schrezenmeir
Jürgen
J
Van Oostveldt
Patrick
P
Huyghebaert
André
A
D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008894:Milk Proteins / Q000378:metabolism / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D000067816:Whey Proteins
D000596:Amino Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D008894:Milk Proteins; D000067816:Whey Proteins; C121294:lactokinins; D002216:Captopril; D007703:Peptidyl-Dipeptidase A