Degradation of angiotensin I to [des-Asp1]angiotensin I by a novel aminopeptidase in the rat hypothalamus.
The particulate enzyme that degrades angiotensin I (ANG I) to [des-aspartate1]angiotensin I ([des-Asp1]ANG I) in the hypothalamic homogenate of the rat has been established as a specific aminopeptidase. The major characteristics is its resistance to inhibition by 10(-4) M amastatin, bestatin and EDTA. Among the four amino acyl-beta-naphthylamides (aspartyl, glutamyl-, arginyl- and leucyl-beta-naphthylamide), aspartyl-beta-naphthylamide is the most susceptible substrate of the enzyme; being degraded at twice the rate of arginyl-, and leucyl-beta-naphthylamide, and six times that of glutamyl-beta-naphthylamide. Although the precise role of this aminopeptidase has yet to be determined, its presence establishes the existence of a specific pathway for the degradation of ANG I that bypasses the formation of ANG II. The relationship between degradation and hypertension is shown by our recent findings that the formation of [des-Asp1]ANG I form ANG I in the hypothalamic homogenate of the spontaneously hypertensive rat (SHR) is significantly enhanced, and the findings of other investigators that the production of ANG II by neuronal cultures of the SHR is significantly decreased.
Sim
M K
MK
Department of Pharmacology Faculty of Medicine, National University of Singapore.
Choo
M H
MH
Qiu
X S
XS
D000577:Amides / Q000378:metabolism; D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D007031:Hypothalamus / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
D000577:Amides; C011437:angiotensin I, des-Asp(1)-; D000803:Angiotensin I; D000626:Aminopeptidases; C109065:aminopeptidase X