CHOLECYSTOKININ UP-REGULATION DURING INTESTINAL REPAIR

To determine whether cholecystokinin (CCK), a small intestinal hormone, may have autocrine or paracrine functions, gene regulation in the rat stomach and duodenum has been evaluated following cytotoxic injury. We quantified total RNA, CCK messenger RNA (mRNA), total protein, small and large forms of CCK peptides and gastrin. The stomach and the intestine respond differently. Following cytotoxic injury duodenal total RNA falls (1.5 ± 0.1 vs 0.18 ± 0.04 mg/g P ≤ 0.0001), and cCK mRNA content is depleted (260 ± 23 vs 41 ± 8 pg CCK mRNA/duodenum P ≤ 0.0001), yet there is a paradoxical increase in CCK mRNA concentration (176 ± 20 vs 303 ± 38 pg CCK mRNA/mg total RNA P ≤ 0.01). Increases occurred in both molecular species of CCK peptides evaluated: CCK8 (8 ± 7 vs 26 ± 2 pmole/g P ≤ 0.0001), large forms of CCK (42 ± 4 vs 250 ± 27 pmole/g P ≤ 0.0001). By contrast, in the stomach, only decreases were observed. These data identify sites of anatomical and biosynthetic upregulation during gastrointestinal repair. Changes are dependent upon the length of the period of recovery, differ between stomach and duodenum, and may be age related. Intestinal CCK may have para- and or autocrine roles in addition to its hormone function. © 1992.