Cholecystokinin upregulation 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 less than or equal to 0.0001), and CCK mRNA content is depleted (260 +/- 23 vs 41 +/- 8 pg CCK mRNA/duodenum P less than or equal to 0.0001), yet there is a paradoxical increase in CCK mRNA concentration (176 +/- 20 vs 303 +/- 38 pg CCK mRNA/mg total RNA P less than or equal to 0.01). Increases occurred in both molecular species of CCK peptides evaluated: CCK8 (8 +/- 7 vs 26 +/- 2 pmole/g P less than or equal to 0.0001), large forms of CCK (42 +/- 4 vs 250 +/- 27 pmole/g P less than or equal to 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.
Greenstein
R J
RJ
Mt. Sinai School of Medicine, New York, New York.
Colucci
R D
RD
Ybanez
M M
MM
Zhang
R L
RL
McElhinney
A J
AJ
Bauman
W A
WA
D000818:Animals; D002766:Cholecystokinin / Q000235:genetics* / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008466:Mechlorethamine / Q000633:toxicity*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000378:metabolism; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D014945:Wound Healing / Q000502:physiology
D005755:Gastrins; D012333:RNA, Messenger; D008466:Mechlorethamine; D012313:RNA; D002766:Cholecystokinin; D012844:Sincalide