Hormonal regulation of amino acid transport system N in primary cultures of rat hepatocytes

Abstract

The transport of histidine and glutamine via system N in cultured hepatocytes was found to be subject to hormonal control. This long-term regulation showed the following characteristics.1. The transport capacity for histidine and glutamine (system N) increased slowly in response to the combination of dexamethasone and insulin to about 4-fold that of controls after 18-30 h. A similar time course was found for the stimulation of system N (2.5-fold) by dexamethasone and glucagon. In contrast the uptake of a-aminoisobutyric acid (system A) was rapidly stimulated 3-fold by dexamethasone and insulin and 5-fold by dexamethasone and glucagon within 3 -6 h but decreased towards control rates after 24 h of cultivation in minimal essential medium.2. Dexamethasone, insulin and glucagon each stimulated glutamine uptake about 2-fold in cultures maintained in W/AB 77 medium, while the combination of dexamethasone with either glucagon or insulin resulted in a 3 -4-fold increase.3. Dexamethasone was most effective at about 0.1 pM. Higher concentrations were less efficient. Insulin reached its optimal effect at concentrations above 1 pM.4. Kinetic analysis revealed that the increased capacity of glutamine transport in response to hormones was due to an increase in V,,,, while K,,, was essentially unchanged.5. The hormone-induced stimulation of system N was prevented by cycloheximide. 6. The induced uptake of glutamine was inhibited by excess amounts of asparagine and histidine but not of These results clearly differentiate the hormonal regulation of system N from that of system A.

Roux-en-Y gastric bypass alters small intestine glutamine transport in the obese Zucker rat

“…A potential mechanism for increased glutamine transport after RYGB is the pancreatic hormone glucagon. Glucagon has been shown to increase intestinal glutamine transport severalfold (7). Previous studies have shown glucagon levels are increased after RYGB in both patients and the obese ZR model (14,17).…”

Tumor necrosis factor stimulates amino acid transport in plasma membrane vesicles from rat liver.

“…In hepatocytes isolated from rats treated in vivo with IL-1, the rate of alanine uptake (systems A and ASC) was significantly increased over that seen in hepatocytes from control animals ( 16). TNF administration may also be accompanied by the release of hormonal mediators, such as glucagon and the glucocorticoid hormones, that are known to stimulate system A and system N (8,10,34). Thus, these other cytokines may work together with hormones, such as the glucocorticoids, in an orchestrated fashion to control amino acid transport across the hepatocyte plasma membrane during critical illness.…”

Protein Kinase C-Mediated Phosphorylation of a Single Serine Residue on the Rat Glial Glutamine Transporter SN1 Governs Its Membrane Trafficking

“…An amino acid response element regulating the promoter activity has been demonstrated for SAT2 (Palii et al, 2004), whereas a pH responsive element that has been identified in the 3Ј untranslated region of SN1 increases protein expression during acidosis (Solbu et al, 2005). However, reports showing pronounced effects on V max without changing K m for the system A and/or N activities indicate recruitment of transporters from preexisting intracellular pools (Gebhardt and Kleemann, 1987;Hundal et al, 1987;Lohmann et al, 1998;Ling et al, 2001;Pastor-Anglada et al, 2005). Membrane trafficking constitutes a major regulatory pathway for many transporters, including transporters for dopamine, serotonin, GABA, and glutamate, and is often governed by phosphorylation/dephosphorylation of specific residues on the transporter proteins (for review, see Robinson, 2002;Melikian, 2004).…”