DISTRIBUTION OF PEPTIDYL-GLYCINE ALPHA-AMIDATING MONOOXYGENASE (PAM) ENZYMES IN NORMAL HUMAN LUNG AND IN LUNG EPITHELIAL TUMORS

C-terminal alpha-amidation is a post-translational modification necess ary for the biological activity of many regulatory peptides produced i n the respiratory tract. This modification is a two-step process catal yzed by two separate enzyme activities, both derived from the peptidyl -glycine alpha-amidating mono-oxygenase (PAM) precursor. The distribut ion of these two enzymes, peptidyl-glycine alpha-hydroxylating monooxy genase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase ( PAL), was studied in the normal lung and in lung tumors using immunocy tochemical methods and in sim hybridization. In normal lung the enzyme s were located in some cells of the airway epithelium and glands, the endothelium of blood vessels, some chondrocytes of the bronchial carti lage, the alveolar macrophages, smooth muscle ails, neurons of the int rinsic ganglia, and in myelinated nerves, A total of 24 lung tumors of seven different histological types were studied, All cases contained PAM-immunoreactive cells with various patterns of distribution. All im munoreactive cells were positive for the PHM antiserum but only some o f them for the PAL antiserum. The distribution of PAM co-localizes wit h some other previously described amidated peptides, suggesting that a midation is an important physiological process taking place in the nor mal and malignant human lung tissue.