Identification and expression of prohormone-converting enzymes in the rat stomach.
The conversion of regulatory peptide precursors to their active forms usually involves limited proteolysis that may be mediated by subtilisin-like prohormone convertases (PC). We have examined the representation of this enzyme family in rat gastric mucosa. With the use of polymerase chain reaction, employing primers to conserved sequences, we identified from rat antrum clones corresponding to PC1/3, PC2, PC5, and furin. Northern blots indicated that the mRNAs for PC1/3 and PC2 were substantially more abundant in mucosa compared with muscle, and that there were differences in expression in antrum and corpus. In the antrum a PC1/3 probe identified hands of 3 and 4.5 kb that were of equal intensity and were both increased in fasted rats; in corpus, the latter mRNA species predominated and did not change with fasting. In rats treated with omeprazole, there was a preferential increase in the antral 3-kb 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 candidates for gastric regulatory peptide processing, 2) there is selective processing of the mRNAs encoding prohormone convertases in different gastric cell populations, and 3) the expression of these enzymes is physiologically regulated.
Macro
J A
JA
Physiological Laboratory, University of Liverpool, United Kingdom.
Dimaline
R
R
Dockray
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D045683:Furin; D008297:Male; D008969:Molecular Sequence Data; D009853:Omeprazole / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D011706:Pyloric Antrum / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000201:enzymology*; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D012333:RNA, Messenger; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases; D009853:Omeprazole