IDENTIFICATION AND EXPRESSION OF PROHORMONE-CONVERTING ENZYMES IN THERAT STOMACH

The conversion of regulatory peptide precursors to their active forms usually involves limited proteolysis that may be mediated by subtilisi n-like prohormone convertases (PC). We have examined the representatio n of this enzyme family in rat gastric mucosa. With the use-of polymer ase chain reaction, employing primers to conserved sequences, we ident ified from rat antrum clones corresponding to PC1/3, PC2, PC5, and fur in. Northern blots indicated that the mRNAs for PC1/3 and PC2 were sub stantially more abundant in mucosa compared with muscle, and that ther e were differences in expression in antrum and corpus. In the antrum a PC1/3 probe identified bands of 3 and 4.5 kb that were of equal inten sity and were both increased in fasted rats; in corpus, the latter mRN A species predominated and did not change with fasting. In rats treate d with omeprazole, there was a preferential increase in the antral 3-k b band. In both antrum and corpus, a PC2 probe hybridized with a band of 2.8 kb that increased in omeprazole-treated rats. The data suggest that 1) PC1/3 and PC2 are expressed in antral mucosa and so are candid ates for gastric regulatory peptide processing, 2) there is selective processing of the mRNAs encoding prohormone convertases in different g astric cell populations, and 3) the expression of these enzymes is phy siologically regulated.