RESUMEN
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. MATERIALS AND 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,+).
Asunto(s)
Sistema de Transporte de Aminoácidos A/efectos de los fármacos , Sistemas de Transporte de Aminoácidos/efectos de los fármacos , Factor de Crecimiento Epidérmico/administración & dosificación , Hormona del Crecimiento/administración & dosificación , Intestino Delgado/metabolismo , Intestino Delgado/cirugía , Sistema de Transporte de Aminoácidos A/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Animales , Transporte Biológico , Sinergismo Farmacológico , Glutamina/metabolismo , Íleon/metabolismo , Yeyuno/metabolismo , Masculino , Conejos , Sodio/farmacologíaRESUMEN
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. MATERIALS AND 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,+).