Post‐translational Modification of Peptide Messengers in the Gut

Abstract

Classical methods such as precursor isolation, cell-free translation and pulse-chase experiments have been of limited use in studying biosynthesis of gastrointestinal peptides, because cell populations are generally sparse and intermingled with other cell types, rates of peptide turnover are low, and levels of mRNA are generally low. However, with the advent of recombinant DNA technology, and its application in predicting precursor sequences, the opportunity has arisen for an alternative approach to the study of propeptides. The success of this approach has to some extent resulted in the eclipse of studies of post-translational processing, although they are still of considerable physiological importance. Study of gastrointestinal peptides is proving a fruitful source of information about the mechanisms involved, as is now clear from recent work on the precursors for gastrin, cholecystokinin (CCK) and vasoactive intestinal peptide (VIP).This review will focus upon these three precursors to illustrate the important features and the physiological significance of post-translational processing, and to outline the strategies currently used to identify the structural modifications which take place in the synthesis of the peptides. Examples will also be drawn where appropriate from other precursors.

Effects of Ostertagia ostertagi on gastrin gene expression and gastrin‐related responses in the calf.

“…2B) which was surprising bearing in mind that G-17 normally predominates in the blood of worm-free animals (Reynolds et al 1991). This does, however, support the results of previous work cited, though not described, by Anderson et al (1988) (Dimaline, 1988); (ii) the longer half-life of G-34. In man, the half-life of G-34 is up to 8 times longer than that of G-17, depending upon the method of determination used (Nilsson, 1980), and may be further extended by sulphation (Pauwels, Dockray & Walker, 1987;Dimaline, 1988); and/or (iii) an increase in contribution made by gastrin of duodenal origin.…”

“…This does, however, support the results of previous work cited, though not described, by Anderson et al (1988) (Dimaline, 1988); (ii) the longer half-life of G-34. In man, the half-life of G-34 is up to 8 times longer than that of G-17, depending upon the method of determination used (Nilsson, 1980), and may be further extended by sulphation (Pauwels, Dockray & Walker, 1987;Dimaline, 1988); and/or (iii) an increase in contribution made by gastrin of duodenal origin. In sheep, G-34 accounts for approximately 50% of the total gastrin recovered from the last quarter of the duodenum although the total gastrin content of the latter organ is relatively small (Reynolds et al 1991 (Pearson, 1993), the magnitude of the increase in expression reported here suggests that an increase in synthesis was likely to be the main cause in the parasitized calves.…”

“…The increase in G-34 could have been due to either: (i) preferential release of newly synthesized gastrin prior to completion of post-translational processing. Incomplete processing might have been caused by an actual impairment in processing or the rate of progastrin synthesis and subsequent secretion exceeding the ability of the G cells to process the peptide (Dimaline, 1988); (ii) the longer half-life of G-34. In man, the half-life of G-34 is up to 8 times longer than that of G-17, depending upon the method of determination used (Nilsson, 1980), and may be further extended by sulphation (Pauwels, Dockray & Walker, 1987;Dimaline, 1988); and/or (iii) an increase in contribution made by gastrin of duodenal origin.…”

“…Incomplete processing might have been caused by an actual impairment in processing or the rate of progastrin synthesis and subsequent secretion exceeding the ability of the G cells to process the peptide (Dimaline, 1988); (ii) the longer half-life of G-34. In man, the half-life of G-34 is up to 8 times longer than that of G-17, depending upon the method of determination used (Nilsson, 1980), and may be further extended by sulphation (Pauwels, Dockray & Walker, 1987;Dimaline, 1988); and/or (iii) an increase in contribution made by gastrin of duodenal origin. In sheep, G-34 accounts for approximately 50% of the total gastrin recovered from the last quarter of the duodenum although the total gastrin content of the latter organ is relatively small (Reynolds et al 1991).…”