Identification of threonine 348 as a residue involved in aminopeptidase A substrate specificity.

Aminopeptidase A (APA; EC 3.4.11.

Asp218 participates with Asp213 to bind a Ca2+ atom into the S1 subsite of aminopeptidase A: a key element for substrate specificity.

APA (aminopeptidase A; EC 3.4.11.

Human brain aminopeptidase A: biochemical properties and distribution in brain nuclei.

Aminopeptidase A (APA) generated brain angiotensin III, one of the main effector peptides of the brain renin angiotensin system, exerting a tonic stimulatory effect on the control of blood pressure in hypertensive rats. The distribution of APA in human brain has not been yet studied. We first biochemically characterized human brain APA (apparent molecular mass of 165 and 130 kDa) and we showed that the human enzyme exhibited similar enzymatic characteristics to recombinant mouse APA.

Aminopeptidase A inhibitors as centrally acting antihypertensive agents.

Among the main bioactive peptides of the brain renin-angiotensin system, angiotensin (Ang) II and AngIII exhibit the same affinity for the type 1 and type 2 Ang receptors. Both peptides, injected intracerebroventricularly, cause similar increase in blood pressure (BP). Because AngII is converted in vivo to AngIII, the identity of the true effector is unknown.

Role of angiotensin III in hypertension.

The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III display the same affinity for type 1 and type 2 Ang II receptors. Both peptides, injected intracerebroventricularly, similarly increase blood pressure (BP); however, because Ang II is converted in vivo to Ang III, the identity of the true effector is unknown.