Developmental regulation of epidermal growth factor receptor kinase in rat intestine.

Abstract

Intraluminal epidermal growth factor (EGF) may regulate intestinal growth and function. The ontogeny, localization, and phosphorylation of the EGF receptor in rat small intestine were studied. EGF-receptor phosphorylation was assayed by antiphosphotyrosine Western blot after EGF administration in vivo and EGF incubation to everted sacs in vitro. EGF-receptor abundance and localization were assayed by Western blot and immunofluorescence using anti-EGF-receptor antibodies. In vivo, orogastric EGF enhanced EGF-receptor phosphorylation in newborn rat jejunum and liver. However, intraluminal EGF had no effect on EGF-receptor phosphorylation in adult intestine or liver. In vitro, mucosal EGF stimulated a fourfold increase in EGF-receptor phosphorylation in suckling jejunum but not in weanling or adult jejunum. In Western blot, EGF-receptor abundance was similar in 22-day-old fetal, 8-day-old suckling, and adult jejunum. In both crypt and villus, EGF-receptor was localized to the basolateral membrane but not to the apical membrane in fetal, suckling, and adult jejunum. Mucosal EGF stimulates EGF-receptor phosphorylation in immature but not in mature intestine. These differences are not explained by EGF-receptor abundance or localization and suggest that the greater mucosal permeability of the immature gut may allow EGF to bind to the EGF-receptor in the basolateral membrane to mediate its effects in suckling rat intestine.