Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…This family includes homologs such as aminopeptidases A and N (AP-N: endothelial cell 3.4.11.2). Reflecting distinct activities, the mammalian IRAP/AngIV binding site has many names, oxytocinase, cystinyl aminopeptidase, placental leucine aminopeptidase, gp-160, or vp-165, depending on its independent cloning (Vauquelin et al, 2002a;Albiston et al, 2004a;Nomura et al, 2005;Tsujimoto and Hattori, 2005). Human IRAP/AngIV binding site contains 1025 residues with N-terminal 110-amino acid-long intracellular domain, a 21-residuelong transmembrane segment (111-131), and an 871-residue-long extracellular C-terminal domain (132-1025), which contains the catalytic and zinc binding sites.…”

“…3.4.11.3 also called LNEP for leucyl-N-exopeptidase). IRAP is a Type 2 transmembrane protein of the gluzincin aminopeptidase family (Rogi et al, 1996;Nomura et al, 2005). This family includes homologs such as aminopeptidases A and N (AP-N: endothelial cell 3.4.11.2).…”

Biochemical and enzymatic properties of the M1 family of aminopeptidases involved in the regulation of blood pressure

“…In pre-eclamptic patients, it was reported that while P-LAP/oxytocinase activity is rather stronger than normal when the pre-eclampsia is mild, it decreased progressively with the patient's deterioration. Since vasopressin is associated with hypertension in cases of pre-eclampsia, it is speculated that increased level of vasopressin may initially raise P-LAP/ oxytocinase levels, which counteracts the hypertensive activity of vasopressin and the failure to induce a further rise will cause hypertension in patients with pre-eclampsia [28]. Recently, human chromosome 5q where the P-LAP/ oxytocinase gene is located was identified as a region of susceptibility to pre-eclampsia, further suggesting the significance of P-LAP/oxytocinase in the pathogenesis of preeclampsia [29].…”

Enzymatic Properties of Human Aminopeptidase A

“…For instance, placental leucine aminopeptidase (P-LAP) 2 /insulin-regulated aminopeptidase (IRAP) plays a role in controlling the concentration of uterotonic and vasoactive hormones, such as oxytocin and vasopressin, possibly derived from the fetus at the interface between the fetus and mother and thus preventing premature delivery and pre-eclampsia (4). It has been reported that adipocyte-derived leucine aminopeptidase (A-LAP)/endoplasmic reticulum aminopeptidase is a multifunctional aminopeptidase with roles in the regulation of blood pressure, angiogenesis, the shedding of cytokine receptors, and the presentation of antigens to major histocompatibility complex class I molecules (3).…”