Expression, secretion, and inhibition of angiotensin-converting enzyme in cultured human bronchial epithelial cells.
The purpose of this study was to determine whether angiotensin-converting enzyme is present in cultured human bronchial epithelial cells and which types of epithelial cells possess this enzyme. It is well known that serum promotes squamous differentiation of airway epithelial cell culture in vitro. We found that whole-cell homogenates of both basal (serum-untreated) and squamous-differentiated bronchial epithelial cells degraded hippuryl-L-histidyl-L-leucine, a synthetic substrate for angiotensin-converting enzyme. Analysis of RNA expression by reverse transcription-polymerase chain reaction (RT-PCR) showed the presence of mRNA for angiotensin-converting enzyme in both types of cells. In addition, we found that squamous cells secreted the enzyme into the culture medium more than basal cells did. Angiotensin-converting enzyme inhibitors (imidaprilat, enalaprilat) inhibited the enzyme activity in bronchial epithelial cells with an IC50 of 0.9-3.6 nM. Exogenously added bradykinin was degraded to bradykinin-(1-5), an inactive fragment, in the squamous cell cultures. Our data indicate the presence of angiotensin-converting enzyme in cultured human bronchial epithelial cells and also that the enzyme is secreted by squamous differentiated cells.
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology*; D002478:Cells, Cultured; D004347:Drug Interactions; D015773:Enalaprilat / Q000494:pharmacology; D004847:Epithelial Cells / Q000145:classification / Q000201:enzymology; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan