The role of epidermal growth factor (EGF) in the acute regulation of intestinal transport of electrolytes and glucose was examined. In vivo transport studies were performed in New Zealand White rabbits (500-900 g) using a single-pass perfusion technique. In vitro net fluxes were determined under short-circuited conditions in Ussing chambers. Kinetic parameters of glucose transport in the presence and absence of EGF were measured in brush-border membrane vesicles. In vivo studies showed that the addition of 60 ng/ml EGF to the perfusate resulted in increased absorption of H2O, Na+, Cl-, and glucose from the jejunum. In Ussing chambers, the presence of EGF caused an increase in jejunal net fluxes of glucose-stimulated Na+ and 3-O-methylglucose due to an increase in mucosal-to-serosal movements. Verapamil abolished the EGF effect. In the absence of glucose, net fluxes of Na+ and Cl- were enhanced in the presence of EGF due to a decrease in the serosal-to-mucosal movement of both ions. Verapamil had no effect on this decrease. The incubation of EGF with brush-border membrane vesicles had no effect on either the maximal flux or the Michaelis constant of glucose transport. These results indicate that EGF is capable of regulating absorption of electrolytes and nutrients from the small intestine and suggest a role for this peptide in the control of intestinal transport.

ABSTRACT. The effects of epidermal growth factor (EGF) on postnatal development of intestinal transport and the physical composition of the microvillus membrane were examined. New Zealand White rabbits received EGF (40 pg/kg/d) from d 3 of life to d 17 either intraperitoneally or orogastrically. Intestinal H20, Na' , and glucose absorption expressed per cm of intestine were significantly increased in animals receiving EGF by either route. When EGF was given by the orogastric route, nutrient absorption rates normalized to mucosal DNA were not elevated; thus, increased absorption induced by orogastric EGF appeared to be secondary to mucosal hyperplasia. In contrast, systemic EGF up-regulated cellular nutrient transport. To evaluate at which membrane level these changes occurred, brush border membrane vesicles were isolated from both the jejunum and ileum of control and EGF-treated animals. Rates of Na'-dependent glucose transport into the vesicles revealed that in the ileum systemic EGF up-regulated maximal rates of glucose transport by 54% without affecting the Km. These observations were associated with alterations in the lipid composition and physical properties of the microvillus membrane. EGF-treated animals had significant reductions in membrane cholesterol content and altered ratios of phospholipid subclasses. The net result of these variations was that the microvillus membrane isolated from EGF-treated animals was significantly more fluid than membrane from controls. Thus, these results suggest that EGF modulates development of transport function during the postnatal period both by stimulating mucosal growth and by inducing specific transport processes. Furthermore, these changes are associated with alterations in the physical composition of the microvillus

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