A peptide with high potency and intrinsic activity for stimulating the secretion of corticotropin-like and β-endorphin-like immunoactivities by cultured anterior pituitary cells has been purified f...

https://science.sciencemag.org/content/sci/213/4514/1394.full.pdf

Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin

Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung

The cardiovascular and other actions of angiotensin II (Ang II) are mediated by AT(1) and AT(2) receptors, which are seven transmembrane glycoproteins with 30% sequence similarity. Most species express a single autosomal AT(1) gene, but two related AT(1A) and AT(1B) receptor genes are expressed in rodents. AT(1) receptors are predominantly coupled to G(q/11), and signal through phospholipases A, C, D, inositol phosphates, calcium channels, and a variety of serine/threonine and tyrosine kinases. Many AT(1)-induced growth responses are mediated by transactivation of growth factor receptors. The receptor binding sites for agonist and nonpeptide antagonist ligands have been defined. The latter compounds are as effective as angiotensin converting enzyme inhibitors in cardiovascular diseases but are better tolerated. The AT(2) receptor is expressed at high density during fetal development. It is much less abundant in adult tissues and is up-regulated in pathological conditions. Its signaling pathways include serine and tyrosine phosphatases, phospholipase A(2), nitric oxide, and cyclic guanosine monophosphate. The AT(2) receptor counteracts several of the growth responses initiated by the AT(1) and growth factor receptors. The AT(4) receptor specifically binds Ang IV (Ang 3-8), and is located in brain and kidney. Its signaling mechanisms are unknown, but it influences local blood flow and is associated with cognitive processes and sensory and motor functions. Although AT(1) receptors mediate most of the known actions of Ang II, the AT(2) receptor contributes to the regulation of blood pressure and renal function. The development of specific nonpeptide receptor antagonists has led to major advances in the physiology, pharmacology, and therapy of the renin-angiotensin system.

https://pharmrev.aspetjournals.org/content/pharmrev/52/3/415.full.pdf

International Union of Pharmacology. XXIII. The Angiotensin II Receptors

http://www.jbc.org/content/275/43/33238.full.pdf

A Human Homolog of Angiotensin-converting Enzyme CLONING AND FUNCTIONAL EXPRESSION AS A CAPTOPRIL-INSENSITIVE CARBOXYPEPTIDASE

ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of ami...

Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2.

It has been shown by use of isolated, perfused rat kidneys that hypertensin II is a potent vasoconstrictor substance while hypertensin I is not. Hence it would appear that in intact animals the pressor activity of hypertensin I results from its rapid conversion to hypertensin II. An enzyme which effects this conversion has been procured from horse plasma in a semipurified form by means of ammonium sulfate fractionation and isoelectric precipitation. A method is described for estimating the activity of the enzyme. An example of the use of the preparation in converting purified hypertensin I to hypertensin II has been described.

https://rupress.org/jem/article-pdf/103/3/295/1078767/295.pdf

The preparation and function of the hypertensin-converting enzyme.

Two types of hypertensin have been demonstrated by means of counter-current distribution. The first type is the product of the action of the enzyme, renin, upon its substrate and has been designated hypertensin I. It can be rapidly converted to a second approximately equally pressor compound, hypertensin II, apparently through the action of an enzyme in the plasma which requires halide or nitrate for activation. A highly purified preparation containing horse hypertensins I and II caused an elevation of blood pressure when injected into human beings.

https://rupress.org/jem/article-pdf/99/3/275/1185311/275.pdf

The existence of two forms of hypertensin.

A purified preparation of a polypeptide renin substrate prepared by tryptic degradation of the protein renin substrate has been analyzed by the fluorodinitrobenzene method and after degradation with renin, carboxypeptidase, and phenylisothiocyanate, has been found to possess the amino acid sequence; asp-arg-val-tyr-ileu-his-pro-phe-his-leu-leu-val-tyr-ser. The first 10 of these amino acids constitutes hypertensin I which is released by cleavage of the leucyl-leucine bond by renin. The remaining 4 amino acids, leu, val, tyr, ser, apparently link hypertensin I to the protein renin substrate.

/pdf/the-preparation-purification-and-amino-acid-sequence-of-a-2ug8cqo1sw.pdf

The preparation, purification, and amino acid sequence of a polypeptide renin substrate

Two dipeptides, phenylalanylarginine (Phe-Arg) and serylproline (Ser-Pro), are released sequentially from bradykinin by angiotensin-converting enzyme purified from hog lungs; chloride increases the rate of release of both dipeptides. Using an automated ninhydrin-reagent method, we studied the kinetics of bradykinin hydrolysis. The reaction proceeded in the absence of chloride; however, the addition of chloride increased the rate of hydrolysis by decreasing Km and increasing Vm. The Km values for bradykinin were 3.9 x 10-6M in the absence of chloride and 0.85 x 10-6M in the presence of 0.01m NaCl (optimal concentration). Both of these Km values were well below the value of 30 x 10-6M determined for angiotensin I at its optimal chloride concentration of 0.1M. Hydrolysis of bradykinin had a pH optimum of 7 and was inhibited by low concentrations (10-6M) of ethylenediaminetetraacetic acid or the nonapeptide pyroglutamyl (Pyr)-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro. It is concluded that one enzyme, acting as a dipept...

Hydrolysis of Bradykinin by Angiotensin-Converting Enzyme

The amino acid sequence of horse hypertensin II has been determined by the use of chymotrypsin, the fluorodinitrobenzene method, and stepwise phenylisothiocyanate degradation. The results indicate that the amino acids of hypertensin II are arranged in the following order: asp-arg-val-tyr-iso-hist-pro-phe.

https://rupress.org/jem/article-pdf/104/2/193/1390755/193.pdf

Joseph R. Kahn

Papers

The preparation and function of the hypertensin-converting enzyme.

The existence of two forms of hypertensin.

The preparation, purification, and amino acid sequence of a polypeptide renin substrate

Hydrolysis of Bradykinin by Angiotensin-Converting Enzyme

The amino acid sequence of hypertensin. II.