Mucosa proteolytic activity

The name pepsin was coined by Schwann 125 years ago (Sll). About 35 years ago, Northrop (N9, NIO) obtained a crystalline material from the bovine gastric mucosa exhibiting proteolytic activity below pH 2, which represented highly purified pepsin. 

In subsequent work, Rapp and Burtin (Rla) studied the gastric mucosa extract from 30 controls and 7 cancerous stomachs by immunoelectro-phoresis. In the extracts of cancerous stomachs, the first 2 anodic fractions disappeared, fractions 3, 6, and 7 decreased, while the most centrally located fraction (4) was increased. Three out of five zones of carboxylic esterase activity disappeared in cancer juices, while all of the 4 zones of proteolytic activity were either absent or markedly decreased. The adjacent gastric mucosa, not revealing the carcinomatous infiltration, showed similar abnormalities. 

A recent study, however, has shown that aminopeptidase activity is present on the surface of porcine buccal mucosa, and that various aminopeptidase inhibitors, including amastatin and sodium deoxycholate, reduce the mucosal surface degradation of the aminopeptidase substrate, leucine-enkephalin [149], Since the peptidases are present on the surface of the buccal mucosa, they may act as a significant barrier to the permeability of compounds which are substrates for the enzyme. In addition to proteolytic enzymes, there exist some esterases, oxidases, and reductases originating from buccal epithelial cells, as well as phosphatases and carbohydrases present in saliva [154], all of which may potentially be involved in the metabolism of topically applied compounds. 

Proteolytic enzymes in the respiratory mucosa play important role(s) in the regulation of lung inflammation and remodelling [123, 124], Pulmonary proteolytic enzymes, however, also comprise one of the barriers which pulmonary-administered protein/peptide drugs have to overcome in order to achieve adequate bioavailability [125]. Intriguingly, the pulmonary enzymatic barrier is an aspect that has been little investigated and is poorly understood. Inconsistencies in the data available to date are most likely a result of the use of different techniques (e.g., PCR, immunotechniques and enzyme activity assays), different species and different cell (pheno)types, for example primary cells vs. cell lines. 

Before turning to the strategy adopted in our work, a few of the characteristics of the two proteins are reviewed. The physical and chemical properties of these proteins have been discussed in detail 11, 14). As first shown by Langley, pepsin is present in its inactive form, pepsinogen, in the gastric mucosa. At acid pH, the zymogen is transformed by an autocat-alytic reaction into pepsin, a proteolytic enzyme with an activity optimum at pH 2.0 and a wide specificity 9, 10, 19). Pepsin is rapidly inactivated above pH 6.0, whereas pepsinogen is stable at neutrality 1 If). 

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