Aminopeptidase A: distribution in rat brain nuclei and increased activity in spontaneously hypertensive rats.
Aminopeptidase A is a membrane-bound zinc metalloprotease which cleaves angiotensin II into angiotensin III. Using a new specific aminopeptidase A inhibitor, EC33, we evaluated its enzymatic activity in several microdissected brain nuclei involved in the control of cardiovascular functions and in the pituitary. We compared this distribution with that of the angiotensin I-converting enzyme which converts angiotensin I to angiotensin II. Aminopeptidase A activity was heterogenously distributed with a 150-fold difference between the lowest and the highest levels. The pituitary and the circumventricular organs were the richest source of enzyme, followed by the median eminence, the arcuate nucleus, the area postrema, the choroid plexus and the supraotic and paraventricular nuclei. We did not find any close parallel between aminopeptidase A and angiotensin I-converting enzyme distributions. We examined both enzymatic activities in brain nuclei of spontaneously hypertensive rats. Aminopeptidase A activity was higher in the spontaneously hypertensive rats than in age-matched Wistar Kyoto control rats. The difference was up to 2.5-fold in several brain nuclei involved in the blood pressure regulation; in contrast, no differences in angiotensin I-converting enzyme activity were found in the same regions. The close correspondence between the distribution of aminopeptidase A activity and angiotensin receptors and nerve terminals in the brain associated with the observation that aminopeptidase A activity was overactivated in the spontaneously hypertensive rats suggest that this enzyme may contribute, at least in part, to the regulation of cardiovascular functions by its ability to convert angiotensin II to angiotensin III.
Zini
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INSERM U36, Chaire de Médecine Expérimentale, Collège de France, Paris.
Masdehors
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Lenkei
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Fournie-Zaluski
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Roques
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Corvol
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Llorens-Cortes
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D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D043384:Glutamyl Aminopeptidase; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D007703:Peptidyl-Dipeptidase A