Influence of the lactokinin Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR) on the release of endothelin-1 by endothelial cells

• Published in: Regulatory peptides Vol. 118; no. 1; pp. 105 - 109
• Main Authors: Maes, Wim, Van Camp, John, Vermeirssen, Vanessa, Hemeryck, Mattias, Ketelslegers, Jean Marie, Schrezenmeir, Jürgen, Van Oostveldt, Patrick, Huyghebaert, André
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.04.2004; Amsterdam Elsevier
• Subjects: Amino Acids - metabolism; Amino Acids - pharmacology; Angiotensin converting enzyme inhibition; Angiotensin-Converting Enzyme Inhibitors - metabolism; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Bio-active peptides; Biological and medical sciences; Captopril - pharmacology; Cells, Cultured; Endothelin; Endothelin-1 - metabolism; Endothelin-1 - secretion; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Endothelium, Vascular - secretion; Fundamental and applied biological sciences. Psychology; Lactokinin; Milk Proteins - metabolism; Milk Proteins - pharmacology; Peptidyl-Dipeptidase A - drug effects; Peptidyl-Dipeptidase A - metabolism; Swine; Vertebrates: endocrinology; Whey Proteins; RT; Endothelin; ACE; ET-1; Bio-active peptides; ALPMHIR; PAEC; Lactokinin; Angiotensin converting enzyme inhibition; Endothelial cell; Endothelin 1; Release
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2003.11.005

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 β-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 μM 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.