Human urinary kallikrein can generate angiotensin II from homologous renin substrates.
We previously proposed the "kinin-tensin system," a unique vasoregulatory system that can produce both angiotensin II and kinins. To verify whether tissue kallikrein is a part of this system in humans, we examined the ability of human urinary kallikrein (HUK) to generate angiotensin (ANG) II directly from homologous renin substrates such as purified human angiotensinogen (AOGEN) and authentic human tridecapeptide renin substrate (13 RS). HUK released ANG II not only from ANG I but also directly from both AOGEN and 13RS at an optimum pH of 7.0. The amount of generated ANG II from 7.5 nmol of each of the three substrates at pH 7.0 was as follows: ANG I, 292.7 +/- 67.2; 13 RS, 1951.7 +/- 239.6; AOGEN, 2.2 +/- 0.3 (pmol/3h, n = 3 mean +/- SE). HUK cleaved Phe-His and His-Leu bonds in 13 RS, and Tyr-Ile and Phe-His bonds in ANG I. These results suggest that HUK is a part of the "kinintensin system", i.e., HUK can not only release kinins, but can also generate ANG II mainly through ANG I conversion and from AOGEN, the latter being a minor source of ANG II. Furthermore, HUK may play a role in regulating vascular tone under certain conditions in vivo.
Sasaguri
M
M
Department of Internal Medicine, Fukuoka University School of Medicine, Japan.
Ideishi
M
M
Ogata
S
S
Miura
S
S
Ikeda
M
M
Arakawa
K
K
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis*; D000808:Angiotensinogen / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007610:Kallikreins / Q000378:metabolism* / Q000652:urine; D013379:Substrate Specificity
D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; D007610:Kallikreins