Immunohistochemical studies indicate multiple enteroendocrine cell differentiation pathways in the mouse proximal small intestine.

The enteroendocrine cell system of the mammalian gastrointestinal tract is comprised of at least 16 different subpopulations. Each subpopulation shows a characteristic distribution along both the crypt-villus and cephalo-caudal axes. In both the small intestine and colon of adult mice, multilabel immunohistochemistry has demonstrated that two or more neuroendocrine products can be coexpressed in various combinations in single cells along the crypt-villus axis, suggesting that enteroendocrine phenotypes may be actively regulated. Using bromodeoxyuridine (BrdU) incorporation and multilabel immunohistochemistry, we have previously demonstrated an enteroendocrine cell differentiation pathway consisting of two subpopulations of cells in the mouse proximal small intestine--one involving the sequential expression of substance P, serotonin, and secretin in cells migrating out of the crypts into the villi, and a second involving the expression of substance P and serotonin in cells which remain in the crypts. In this report, we use double label immunohistochemistry and BrdU incorporation to define the temporal and spatial interrelationships between gastrin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and gastric inhibitory peptide (GIP) immunoreactive cells in the mouse proximal small intestine. The expression of these products was compared with that of substance P, serotonin, and secretin. Minimal overlap of expression was found in cells immunoreactive for substance P or serotonin with gastrin, CCK, GLP-1, or GIP; however, secretin was found colocalized in villus-associated gastrin, CCK, and GLP-1 containing cells.(ABSTRACT TRUNCATED AT 250 WORDS)