Implication of Opioid Receptors in the Antihypertensive Effect of a Bovine Casein Hydrolysate and αs1-Casein-Derived Peptides

The antihypertensive activity of two alpha(s1)-casein-derived peptides and casein hydrolysate containing these sequences was evaluated in the presence of naloxone. The activity was abolished by this opioid antagonist at 2, 4, and 6 h postadministration. Similarly, the antihypertensive effect of the alpha(s1)-casein peptides (90)RYLGY(94) (-23.8 +/- 2.5 mmHg) and (143)AYFYPEL(149) (-21.1 +/- 3.2 mmHg) at 5 mg/kg of body weight was antagonized by the co-administration of naloxone. Because peptide (143)AYFYPEL(749) had recently shown opioid activity, a molecular dynamic simulation of this peptide with human p-opioid receptor was performed to demonstrate its favorable structure and interaction energy, despite the presence of Ala at the N terminus. Altogether, these results revealed that the in vivo effect on systolic blood pressure of the studied alpha(s1)-casein peptides is mediated by interaction with opioid receptors and the antihypertensive activity of casein hydrolysate can be very likely ascribed to them with the possible contribution of other mechanisms.