Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have utilized canalicular (cLPM) and basolateral (blLPM) liver plasma membrane vesicles to investigate the domain localization of several Na(+)-dependent amino acid transporters. Neutral amino acid transport by systems N and ASC was measurable in both domains but was greater in blLPM vesicles. Sodium-dependent glutamate uptake (system X-) was preferentially localized to cLPM. The absolute activity and domain distribution of these three carriers remained unchanged after treatment of rats with a combination of glucagon and dexamethasone. A low level of basal system A activity was present in both the blLPM and cLPM. Glucagon-induced system A activity was first observed in blLPM vesicles approximately 60 min posthormone treatment and, in cLPM vesicles, approximately 30 min later. In situ perfusion of glucagon-treated rat liver with the membrane-impermeant protein modification reagent glutathione maleimide specifically inactivated blLPM system A activity and abolished the delayed arrival of hormone-induced activity to the cLPM. Transient perfusion of the liver with glutathione maleimide followed by a recovery period in vivo showed that the reagent did not irreversibly inactivate the transcytotic process and also provided an independent demonstration of the time delay between arrival of the carrier activity at the two membrane surfaces. These results support the concept of a transcytotic process in which the blLPM is the sorting site for the hormone-induced system A carrier proteins that eventually reach the cLPM.
 ...
PMID:Plasma membrane domain localization and transcytosis of the glucagon-induced hepatic system A carrier. 133 91

Poly(A)+ RNA (mRNA) isolated from rat liver was injected into Xenopus laevis oocytes, and expression of Na+/L-alanine transport was assayed by measuring Na(+)-dependent uptake of L-[3H]alanine. Expression of Na+/L-alanine transport was detected 3-7 days after mRNA injection, and was due to an increment of the Na(+)-dependent component. After injection of 40 ng of total mRNA, Na(+)-dependent uptake of L-alanine was 2.5-fold higher than in water-injected oocytes. In contrast with Na+/L-alanine transport by water-injected oocytes, expressed Na+/L-alanine transport was inhibited by N-methylaminoisobutyric acid, was inhibited by an extracellular pH of 6.5 and was saturated at approx. 1 mM-L-alanine. After sucrose-density-gradient fractionation, highest expression of Na+/L-alanine uptake was observed with mRNA of 1.9-2.5 kb in length. Compared with mRNA isolated from control rats, mRNA isolated from glucagon-treated rats showed a approx. 2-fold higher expression of Na+/L-alanine transport. The results demonstrate that both liver Na+/L-alanine transport systems (A and ASC) can be expressed in X. laevis oocytes. Furthermore, the data obtained with mRNA isolated from glucagon-treated rats suggest that glucagon regulates liver Na+/L-alanine transport (at least in part) via the availability of the corresponding mRNA.
 ...
PMID:Expression of rat liver Na+/L-alanine co-transport in Xenopus laevis oocytes. Effect of glucagon in vivo. 239 79

The specific transport mechanisms that mediate the hepatic uptake of L-[3H]alanine and of an unnatural homologue, alpha-[14C]methylaminoisobutyric acid (MeAIB), were analyzed in hepatocyte suspensions from Raja erinacea. Aminooxyacetate, an inhibitor of aminotransferase activity was used to prevent alanine metabolism. After 3 h of incubation with either 0.5 mM alanine or MeAIB, hepatic concentrations of these amino acids were significantly higher in the presence than absence of Na+ (8 vs. 1 and 1 vs. 0.1 mM, respectively). Kinetic studies indicated that both alanine and MeAIB transport occurred via sodium-dependent saturable mechanisms. [14C]MeAIB uptake was completely inhibited by excess L-alanine. Uptake of [3H]alanine was inhibited by a 40-fold excess of serine and cysteine (53-54%), by MeAIB and methylalanine (26-31%), and by leucine (14%), whereas D-alanine, beta-alanine, taurine, and glutamate had no effect. Insulin and glucagon were unable to stimulate [3H]alanine uptake. Glucose release from hepatocytes was unaffected by 10 mM alanine or 2 mM aminooxyacetate, indicating that alanine is not a major gluconeogenic precursor in this marine elasmobranch. These results suggest that uptake of L-alanine by skate hepatocytes occurs predominantly via a sodium-dependent system, with properties similar to those exhibited by the ASC neutral amino acid transport system previously characterized in Ehrlich ascites tumor cells and rat hepatocytes.
 ...
PMID:Characteristics of L-alanine uptake in freshly isolated hepatocytes of elasmobranch Raja erinacea. 336 8

Plasma membrane vesicles prepared from intact rat liver or isolated hepatocytes retain transport activity by systems A, ASC, N, and Gly. Selective substrates for these systems showed a Na+-dependent overshoot indicative of energy-dependent transport, in this instance, driven by an artificially-imposed Na+ gradient. Greater than 85% of Na+-dependent 2-aminoisobutyric acid (AIB) uptake was blocked by an excess of 2-(methylamino)isobutyric acid (MeAIB) with an apparent Ki of 0.6 mM. Intact hepatocytes obtained from glucagon-treated rats exhibited a stimulation of system A activity and plasma membrane vesicles isolated from those same cells partially retained the elevated activity. Transport activity induced by substrate starvation of cultured hepatocytes was also evident in membrane vesicles prepared from those cells. The membrane-bound glucagon-stimulated system A activity decays rapidly during incubation of vesicles at 4 degrees C (t1/2 = 13 h), but not at -75 degrees C. Several different inhibitors of proteolysis were ineffective in blocking the decay of transport activity. Hepatic system N transport activity was also elevated in plasma membrane vesicles from glucagon-treated rats, whereas system ASC was essentially unchanged. The results indicate that both glucagon and adaptive regulation cause an induction of amino acid transport through a plasma membrane-associated protein.
 ...
PMID:Maintenance of glucagon-stimulated system A amino acid transport activity in rat liver plasma membrane vesicles. 396 88

System A-mediated amino acid transport in liver tissue is stimulated by diabetes or by exogenous glucagon. The present report describes the decay process for stimulated System A activity in isolated rat hepatocytes. Transport induced by glucagon, insulin, or spontaneous diabetes (BB/G rats) decayed rapidly after initiation of primary cultures; the estimated half-life was about 1.5 h. In contrast, the stimulated activity in cultured hepatocytes from streptozotocin-diabetic rats had a half-life of about 2.5 h. It is not known if the loss of System A activity is the result of proteolysis or of another form of inactivation. The decay was blocked by either actinomycin or cycloheximide, but was unaffected by leupeptin, methylamine, chloroquine, dinitrophenol, rotenone, or tunicamycin. Studies with cycloheximide and actinomycin suggest the following: 1) within 30 min after initiation of cell cultures, synthesis of the corresponding mRNA for the transport-inactivating protein has begun; 2) the mRNA for transport-inactivating protein is relatively long-lived, but the inactivating protein itself has a half-life of less than 1 h; and 3) actinomycin blocks the decay through inhibition of transport-inactivating protein biosynthesis rather than by protection of the mRNA for the protein responsible for System A activity. A working model for the synthesis and decay of System A activity is presented. Cationic amino acid transport, System y+, was also stimulated severalfold after induction of diabetes or glucagon injection of rats. Systems ASC, X-, and N were enhanced to varying degrees in hepatocytes from diabetic or glucagon-injected rats, but the level of stimulation for each was not as great as that found for Systems A or y+.
 ...
PMID:Induction and decay of amino acid transport in the liver. Turnover of transport activity in isolated hepatocytes after stimulation by diabetes or glucagon. 620 Apr 77

The effects of insulin, glucagon of Dexamethasone (DEX) and of glucagon with insulin or DEX were examined on the uptake of 2-amino [1-14C]isobutyric acid (AIB) and N-Methyl-2-amino [1-14C]isobutyric acid (NMe AIB) in monolayer cultures of rat hepatocytes. Insulin and glucagon stimulated the uptake of both the amino acids and DEX inhibited it, showing that all three of these hormones regulate the A system (the sodium-dependent system that permits the transport of NMe AIB) for amino acid transport in these cultures. Experiments investigating the transport of aminocyclopentane-1-carboxylic acid, 1- [carboxyl-14C] in the presence of excess AIB or in the absence of sodium showed that insulin had no effect on the activity of the L system (the sodium-independent system that prefers leucine). Experiments on the uptake of AIB in the presence of excess NMe AIB showed insulin had no effect on the transport activity of the ASC system (the sodium-dependent system that does not transport NMe AIB). Insulin concentrations ranging from 0.1 nM to 100 nM did not antagonize the stimulatory effect of optimum or suboptimum concentrations of glucagon on the uptake of either AIB or NMe AIB. Similarly, glucagon did not antagonize the stimulatory effect of optimum or suboptimum concentrations of insulin on the uptake of both the amino acids. The combined effect of insulin and glucagon was additive on the rate as well as the cumulative uptake of both AIB and NMe AIB. DEX alone inhibited the transport of both AIB and NMe AIB by about 25%, while glucagon caused a 2--3-fold increase; however, the addition of glucagon to cultures containing DEX caused a 7--8-fold increase in the uptake of both AIB and NMe AIB when compared to cultures containing DEX alone. The effect of insulin on the levels of cAMP was also investigated. Insulin had no effect on the cAMP levels in cultures treated or untreated with optimum or suboptimum concentrations of glucagon.
 ...
PMID:Hormonal regulation of amino acid transport and cAMP production in monolayer cultures of rat hepatocytes. 625 4

The present report shows that System A-mediated 2-aminoisobutyric acid (AIB) uptake is elevated in hepatocytes isolated from adrenalectomized rats when they are compared to control cells. Although System ASC activity also shows this perturbation, Systems N, beta, L1, and L2 are unaffected. Transport of AIB in both cell types is stimulated by dexamethasone, insulin, and glucagon, yet the hepatocytes from the adrenalectomized rats are much less responsive to these hormones. This apparent decrease in competence is seen for adaptive regulation of System A as well. The in vitro addition of dexamethasone to the hepatocytes from the adrenalectomized animals does not restore fully their ability to respond to hormones or amino acid deprivation. These effects are observed even after the cells have been held in primary culture for 24 hr. The simultaneous addition of glucagon and dexamethasone to either cell type resulted in stimulation of transport to rates significantly greater than the sum of the increases produced by the two hormones when added separately. In contrast, insulin and dexamethasone were additive in their effects rather than synergistic. These results suggest that hepatocytes from adrenalectomized rats are less competent than control cells with respect to regulation of neutral amino acid transport, including stimulation by insulin or amino acid starvation, two processes which appear not to depend on glucocorticoid for maximal response.
 ...
PMID:Regulation of neutral amino acid transport in hepatocytes isolated from adrenalectomized rats. 633 22

Primary cultures of rat hepatocytes respond to hormones or amino acid deprivation by increasing System A-mediated neutral amino acid transport. Previous reports have shown this stimulation to be dependent on RNA and protein synthesis, whereas the present report describes the inhibition of System A by tunicamycin (TM), an inhibitor of asparagine-linked glycoprotein biosynthesis. The basal System A activity, as monitored by Na+-dependent 2-aminoisobutyric acid uptake, was decreased by TM when hepatocytes were cultured for 24 h in the presence of the antibiotic. System Gly activity was also sensitive to TM, whereas the activities of Systems L1, L2, and N were relatively resistant and that of System ASC was only moderately affected. The increase in System A-mediated uptake after incubation of hepatocytes in the absence of amino acids (i.e. adaptive control) was almost completely abolished by including TM. Likewise, stimulation of hepatic 2-aminoisobutyric acid transport by glucagon, dexamethasone, insulin, or vasopressin was also blocked by the inhibitor. When glucagon alone or glucagon plus dexamethasone was added, the inhibition by TM was transient such that the degree of inhibition decreased with incubation time after the initial 2 h. Addition of TM to cells which had been treated previously for 2 h to 4 h with glucagon and dexamethasone blocked any further increase in transport indicating that the glycoprotein component of System A must be continually synthesized to sustain the increase in activity. Treatment of hepatocytes with various lectins did not inhibit 2-aminoisobutyric acid transport.
 ...
PMID:Induction of amino acid transport system A in rat hepatocytes is blocked by tunicamycin. 635 4

Primary cultures of adult rat hepatocytes were used to study the effects of 100 mM ethanol on various neutral amino acid transport systems. Ethanol exposure for 24 h selectively decreased amino acid uptake by the A and N systems by 40-70%, but had no significant effect on the ASC and L systems. The decrease in the A system was significant after 3 h of ethanol exposure, and the activity was not affected by the presence or absence of ethanol during the uptake measurements. Kinetic analysis showed that ethanol treatment affected predominantly the high-affinity component of A system activity by decreasing the apparent Vmax without significantly changing the apparent Km. Ethanol treatment did not prevent the cells from increasing A system activity in response to insulin and glucagon, but the magnitude of hormone-stimulated uptake was reduced.
 ...
PMID:Ethanol treatment selectively decreases neutral amino acid transport in cultured hepatocytes. 647 6

We find that the two wide-range Na+-dependent transport systems A and ASC for various neutral amino acid can be discriminated more sharply in the hepatoma cell line HTC than in any cell yet studied by us in which the two systems co-exist. The gain comes partly from a higher reproducibility and a higher relative ASC rate for HTC than in ordinary rat hepatocytes, also a repressed condition of System A unless first deprived of amino acids, but mainly from our finding that in the hepatoma cell threonine serves as a nearly specific substrate and inhibitor of System ASC, thus decisively supplementing older discriminatory techniques. In ordinary hepatocytes cysteine is quite specific to ASC as a substrate but not as an inhibitor, whereas threonine is specific in neither role. In the hepatoma cell cysteine in turn is specific in neither role. In addition to these and other differences between the two cells in analog specificity, which are partly assignable to System ASC and partly to System A, System ASC of the hepatoma cell shows an inhibition on lowering the pH from 6.5 to 5 not seen in the ordinary hepatocyte. Furthermore, threonine uptake by the hepatoma cell undergoes no stimulation when Li+ is substituted for choline in a Na+-free medium, whereas ASC uptake by the ordinary rat hepatocyte is stimulated much as is System A uptake. As in other occurrences, and in contrast to System A, ASC transport in the hepatoma cell is stimulated neither by amino acid deprivation nor by insulin, glucagon, or dexamethasone. Trans-stimulation, both inward and outward, via System ASC is vigorous in the hepatoma cell. Despite the surprising differences observed, common features of each system in various occurrences continue to justify the use of the abbreviations ASC and A as long as they are understood as generic designations.
 ...
PMID:Surprising differences in substrate selectivity and other properties of systems A and ASC between rat hepatocytes and the hepatoma cell line HTC. 679 May 28


1 2 Next >>