Hemorphins derived from hemoglobin have an inhibitory action on angiotensin converting enzyme activity

Abstract

The hemorphins are opioid active peptides, which are enzymatically released from the beta-chain of hemoglobin. In this paper we report an inhibitory effect of these peptides on angiotensin converting enzyme (ACE) activity, known to be involved in blood pressure regulation. The hemorphins were found to be quite stable in tissue extracts containing ACE, and their importance as naturally occurring ACE inhibitors is discussed.

Generation of VV‐hemorphin‐7 from globin by peritoneal macrophages

“…The actual pathway by which VV-hemorphin-7-peptide might be generated and involved physiologically is presently not fully elucided. Some authors have already demonstrated the potent role of hemorphins toward endorphins [15,16] and Angiotensin Converting Enzyme (ACE) [13,14]. These last authors suggested that these opioid-like peptides might act both on blood pressure regulation via ACE and on analgesic strength via opioid receptors during physiological and/or pathologic degradation of hemoglobin [l 3].…”

“…Since several hemorphins have been found in rive [3,9] and characterized by their biological properties [13,17], it will be of great interest to find out all the metabolic pathways from hemoglobin to hemorphins. Moreover, Carraway et al suggested the existence of a putative endogenous processing, similar to the renin-angiotensin system, which generates neurotensin-and enkephalin-related peptides in blood circulation [27,28].…”

“…This inhibition was reversed by the specific opioid antagonist, naloxone [11,12]. In addition to this effect, the hemorphins exhibit inhibitory action on angiotensin converting enzyme [13,14]. Another interesting feature of some hemorphins is their effect on 13-endorphin release from the pituitary [15].…”

Isolation and characterization of a bradykinin‐potentiating peptide from a bovine peptic hemoglobin hydrolysate

“…Such correlations have already been noted between ACE inhibitors from bovine casein hydrolysate and casomorphin [13]. derived peptides since one of them, the opioid active fragment LVV-hemorphin-6 [10] was also recently described as an ACE inhibitor [9]. A comparison between the ~-chains of bovine and human hemoglobin revealed that the hexapeptides located in position 129-134 differ only in one amino acid: Leu.Ala-Asn-Val-Ser-Thr (bovine) versus Leu-Ala-SerVal-Ser-Thr (human).…”

“…Recently, a peptide called LVV-hemorphin-6, corresponding to the sequence at position 32-40 of the tchain of the human hemoglobin, was reported to inhibit ACE activity [9]. This peptide was orif~;nally isolated from the human pituitary gland [10].…”