Differential distribution of molecular forms of cholecystokinin in human and porcine small intestinal mucosa.

To examine the distribution of cholecystokinins (CCKs) along the small intestine we examined the nature of CCKs in samples of jejunum, mid-intestine and ileum from human and porcine intestine. CCKs in intestinal mucosa were extracted by boiling in both neutral and acid conditions, and subjected to high pressure liquid chromatography (HPLC) to separate the forms of CCK followed by radioimmunoassay of separate fractions. In neutral extracts of human intestine CCK immunoreactivity totalled 119.4, 22.9 and less than 1 ng/g in jejunum, mid-intestine and ileum, whilst in acid extracts the corresponding values were 65.3, 47.4 and less than 1 ng/g. Amounts of CCK extracted from porcine mucosa were of similar magnitude. In neutral extracts material co-chromatographing on HPLC with synthetic porcine CCK 8 predominated, whilst in acid extracts material co-chromatographing with CCKs 33/39 was the major form. These forms of human and porcine CCKs extracted from the mucosa behaved similarly to CCK 8 and CCK 33/39 standards on HPLC, in the radioimmunoassay and on molecular exclusion chromatography - suggesting marked similarity of the CCKs in the two species. In both species there was a marked change in the ratios of CCK 8: CCK 33/39 down the intestine from 1: 0.8 in human jejunum to 1: 5.6 in mid-intestine and from 1: 1.5 in porcine jejunum to 1: 5.8 in mid-intestine. These observations may explain the changing patterns of CCKs in circulation with time after ingestion of a fat meal and the greater impairment of CCK 8 than CCK 33/39 release observed in coeliac disease.