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


METHODS
New Zealand White rabbits underwent 70% small bowel resection then immediately received parenteral EGF, GH, both EGF and GH, 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 B(0) was 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 B(0) 71%) and ileum (A 13%, B(0,+) 27%, and B(0) 60%). Na(+)-dependent GLN uptake was reduced by one 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, there was 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 a result of a 6.1-8.2-fold increase in system A as well as a 3.8-3.9-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, USA.
Avissar
Nelly E
NE
Vukcevic
Dubravka
D
Toia
Liana
L
Ryan
Charlotte K
CK
Berlanga-Acosta
Jorge
J
Sax
Harry C
HC
D026924:Amino Acid Transport System A / Q000187:drug effects* / Q000378:metabolism; D026905:Amino Acid Transport Systems / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D005973:Glutamine / Q000378:metabolism; D013006:Growth Hormone / Q000008:administration & dosage*; D007082:Ileum / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism* / Q000601:surgery*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology
D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems; D005973:Glutamine; D004815:Epidermal Growth Factor; D013006:Growth Hormone; D012964:Sodium