Growth factor enhancement of intestinal function: dramatic response but lack of synergism.
OBJECTIVE
The authors have shown that gastrin and epidermal growth factor (EGF) exert a trophic effect on intestinal epithelial cells. Because these peptides may have different mechanisms by which they stimulate these cells, this study was designed to determine the effect of gastrin and EGF on the intestinal epithelial cell and to evaluate their potential synergistic effect.


METHODS
Twenty young adult male Sprague-Dawley rats underwent placement of jugular venous catheters that were connected to subcutaneously placed osmotic minipumps. The rats were divided into four groups based on the content of the osmotic pump: Group 1, saline (control, n = 5); Group 2, EGF at 150 microg/kg/d (n = 5); Group 3, gastrin at 13.5 nmol/kg/d (n = 5); and Group 4, EGF at 150 microg/kg/d plus gastrin at 13.5 nmol/kg/d (n = 5). After a 14-day intravenous infusion, [C14] galactose and [C14] glycine absorption (pmol/cm2 intestine), mucosal DNA content (microg/mg mucosa), and protein content (microg/mg mucosa) were measured in the small intestine of each rat.


RESULTS
The galactose absorption, glycine absorption, DNA content, and protein content were significantly increased by EGF (69%, 28%, 64%, and 55%, respectively) and gastrin (72%, 60%, 93%, and 48%, respectively) when compared with control. Combining EGF and gastrin also significantly increased these parameters (61%, 44%, 96%, and 70%, respectively) when compared with control. However, these data demonstrate no further enhancement than the effect of each peptide alone.


CONCLUSIONS
EGF and gastrin individually may be useful for patients who have inadequate intestinal function, but when combined did not exert a synergistic benefit.
Kato
Y
Y
Dupont Hospital for Children, Wilmington, DE 19899, USA.
Yu
D
D
Schwartz
M Z
MZ
D000704:Analysis of Variance; D000818:Animals; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005755:Gastrins / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005755:Gastrins; D005765:Gastrointestinal Agents; D004815:Epidermal Growth Factor