Aminopeptidase P (AmP) is an aminoacylproline hydrolase capable of degrading oligopeptides having the N-terminal sequence X-P-P- (as occurs in bradykinin (BK): R-P-P-G-F-S-P-F-R). AmP, part of which is disposed on endothelium, clearly plays a role in the inactivation of circulating BK in rats and guinea pigs but appears to be effectively absent from endothelia of cats and rabbits. To help clarify its possible function as a kininase in humans, we have examined for AmP mRNA in sixteen human tissues by northern blotting. Recently, we have cloned human AmP cDNA and have used a 1,068 bp fragment of the latter as a probe. The cDNA probe encodes the protein sequence extending from amino acid residue 123 to 478. Poly A-RNA was used for each tissue; Mr of AmP mRNA was 3.5 kd. The descending rank order for intensity of blots was kidney > small intestine ≇ liver > placenta ≇ heart ≇ colon mucosa > prostate ≇ lung ≇ skeletal muscle. Intensities of blots using lung RNA were variable, possibly indicative of mRNA instability. RNAs of spleen, thymus, testis, ovary, brain, peripheral blood leukocytes and pancreas were apparently unreactive with the probe. Human lymphocytes have AmP catalytic activity, as do human aortic, pulmonary artery and pulmonary microvascular endothelial cells. Thus, the tissue RNAs unreactive by northern blotting should be retested by RT-PCR to examine for low abundance AmP mRNA. Although northern blotting has relatively poor lower limits of detection, our results indicate that AmP is widely distributed among human tissues and is therefore a likely kininase under physiologic conditions.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Molecular Biology