Growth hormone and epidermal growth factor together enhance amino acid transport systems B(0,+) and A in remnant small intestine after massive enterectomy.
BACKGROUND
Sodium-dependent brush border nutrient transport is decreased 2 weeks after massive enterectomy. This downregulation is ameliorated by a 1-week infusion of parenteral growth hormone (GH) and epidermal growth factor (EGF) started 1 week after resection. We hypothesized that glutamine (GLN) transport would be enhanced by earlier and longer growth factor infusion, with differential effects on the Na(+)-dependent GLN transport systems A, B(0,+), and B0/ASCT2.


METHODS
New Zealand White rabbits underwent 70% small bowel resection then immediately received parenteral EGF, GH, both, or neither for 2 weeks. Na(+)-dependent 3H-GLN uptake by jejunal and ileal brush-border membrane vesicles was measured and the contribution of systems A, B(0,+), and B0 then determined by competitive inhibition. Data were analyzed using one-way analysis of variance.


RESULTS
In nonresected animals, the relative contribution of the systems was similar in jejunum (A, 9%, B(0,+), 20%; and B0, 71%) and ileum (A, 13%; B(0,+), 27%; and B0, 60%). Na(+)-dependent GLN uptake was reduced by half in resected, untreated controls, primarily because of decreased B(0) activity. EGF or GH alone did not affect Na(+)-dependent GLN transport, but as a combination, increased uptake in the residual ileum and jejunum by 144% and 150%, respectively, over resected controls (P<0.05). This was twice that achieved by delayed and shorter-duration combination treatment. This augmentation was due to a 6.1- to 8.2-fold increase in system A as well as a 3.8- to 3.9-fold enhancement of system B(0,+) activity in remnant ileum and jejunum (P<0.01).


CONCLUSIONS
Parenteral EGF and GH, given in combination for 2 weeks immediately after massive enterectomy, synergistically enhance GLN uptake by systems A and B(0,+).
Ray
Edward C
EC
Department of Surgery, University of Rochester Medical Center, Rochester, New York 14642, USA.
Avissar
Nelly E
NE
Vukcevic
Dubravka
D
Toia
Liana
L
Ryan
Charlotte K
CK
Berlanga-Acosta
Jorge
J
Sax
Harry C
HC
D000222:Adaptation, Physiological / Q000187:drug effects* / Q000502:physiology; D026905:Amino Acid Transport Systems / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D013505:Digestive System Surgical Procedures; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects* / Q000502:physiology / Q000601:surgery*; D008297:Male; D023421:Models, Animal; D011817:Rabbits
D026905:Amino Acid Transport Systems; D019382:Human Growth Hormone; D004815:Epidermal Growth Factor