GLUCOCORTICOID REGULATION OF SPLANCHNIC GLUTAMINE, ALANINE, GLUTAMATE, AMMONIA, AND GLUTATHIONE FLUXES

Interorgan glutamine and associated metabolite fluxes were measured ac ross the gut and liver to delineate splanchnic bed fluxes secondary to enhanced arterial loads mobilized in the periphery by glucocorticoid. Experiments were performed on adrenalectomized rats since adrenalecto my doubled the hepatic glucocorticoid receptor population compared wit h intact animals. Under these conditions, triamcinolone supplement (40 mug.day-1.100 g body wt-1) enhanced the combined net glutamine uptake by gut and liver eightfold, whereas combined gut and liver unidirecti onal breakdown and synthesis fluxes both increased (3.4- and 7.4-fold, respectively). Triamcinolone supplement also altered the pattern of m etabolite released; gut released predominantly ammonium and some alani ne, whereas the liver removed more alanine along with glutamine and re leased more urea, glutamate, and glutathione. Mechanistically, enhance d cellular glutamine uptake could be attributed to a three- to fourfol d acceleration of glutamine transport associated with a rise in intrac ellular glutamine content. However, uptake by isolated membrane vesicl es revealed only a small (27%) increase in System N activity, whereas extraction and reconstitution of the transporter into proteoliposomes failed to demonstrate increased transporter activity. Similarly, activ ity of phosphate-dependent glutaminase and glutamate dehydrogenase inc reased in crude homogenates (2-fold), but the former disappears in com pletely disrupted preparations. Furthermore, whereas messenger RNA and assayable enzymic activity for glutamate dehydrogenase clearly increa sed with glucocorticoid, glutaminase message was less significantly in creased. Thus glucocorticoid appears directly capable of accelerating hepatic glutamine extraction primarily by modulating transporter activ ity that is closely coupled to glutamine utilization.