Somatostatin inhibits insulin-stimulated amino acid uptake into cultured rat myoblasts

1987 ◽  
Vol 114 (4) ◽  
pp. 470-474 ◽  
Author(s):  
G. S. G. Spencer ◽  
D. J. Hill ◽  
G. J. Garssen ◽  
J. P. G. Williams
Keyword(s):  
Amino Acid ◽  
Nutrient Uptake ◽  
Monolayer Culture ◽  
Amino Acid Uptake ◽  
Inhibitory Effect ◽  
Isobutyric Acid ◽  
Acid Uptake ◽  
Newborn Rat ◽  
Amino Isobutyric Acid

Abstract. The effects of somatostatin on the acute metabolic actions of insulin on newborn rat myoblasts in culture has been examined during monolayer culture. Somatostatin significantly inhibited the insulin-stimulated uptake of [3H]leucine and [3H]amino-isobutyric acid into myoblasts but had no effect on basal (unstimulated) uptake of these two substances. The lowest concentration of somatostatin to have a significant effect was 10 μg/l, and this was apparent in all the experiments undertaken. The inhibitory effect of somatostatin was seen at all effective concentrations of insulin used (0.3–1 U/l). These findings lend support to the concept of an endocrine role for somatostatin in vivo and suggest that a peripheral antagonism may exist between circulating insulin and somatostatin on anabolic processes such as nutrient uptake into cells.

scholarly journals Studies on Aromatic Amino Acid Uptake by Rat Brain in Vivo

1962 ◽  
Vol 237 (3) ◽  
pp. 803-806
Author(s):  
Gordon Guroff ◽  
Sidney Udenfriend
Keyword(s):  
Amino Acid ◽  
Rat Brain ◽  
Aromatic Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake

Hepatic Amino Acid Uptake Is Decreased in Lactating Rats. In Vivo and In Vitro Studies

1994 ◽  
Vol 124 (11) ◽  
pp. 2163-2171 ◽  
Author(s):  
José García de la Asunción ◽  
Amparo Devesa ◽  
Juan R. Viña ◽  
Teresa Barber
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
In Vitro Studies ◽  
Acid Uptake

Lack of effects of hypothermia on cerebral amino acid uptake in vivo

1977 ◽  
Vol 125 (1) ◽  
pp. 187-191 ◽  
Author(s):  
Emirbek Z. Emirbekov ◽  
Henry Sershen ◽  
Abel Lajtha
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake

Placental amino acid uptake. VI. Regulation by intracellular substrate

1982 ◽  
Vol 243 (1) ◽  
pp. C46-C51 ◽  
Author(s):  
R. B. Steel ◽  
C. H. Smith ◽  
L. K. Kelley
Keyword(s):  
Amino Acid ◽  
Placental Tissue ◽  
Membrane Vesicles ◽  
Amino Acid Uptake ◽  
Maternal Plasma ◽  
Acid Uptake ◽  
L System ◽  
Intracellular Amino Acids ◽  
Human Placental Tissue

Amino acid uptake by human placental tissue is regulated by intracellular amino acids. alpha-Aminoisobutyric acid (AIB) uptake was reduced at intracellular AIB concentrations of 0.8 mM. The magnitude of reduction increased sharply between 1 and 3 mM and reached a maximum of 45% at 5 mM. Suppression was specific to the "A" system. It occurred only when both the amino acid used for preloading and that used as an uptake substrate were active with that system. In the "L" system, facilitation apparently occurs, and in the "ASC" system there is no apparent effect. The system specificity as well as other evidence indicated that suppression is caused by substrate present intracellularly rather than by dilution of extracellular substrate. Suppression was independent of inhibitors of protein synthesis and was not seen in membrane vesicles prepared from preloaded tissue, indicating that intracellular substrate interacts directly with the carrier (transinhibition) rather than altering its synthesis or degradation. The A system transinhibition has the potential to regulate syncytial uptake in vivo and limit variation due to changes in maternal plasma amino acid concentration.

scholarly journals Alanine uptake activates hepatocellular chloride channels

1997 ◽  
Vol 273 (4) ◽  
pp. G849-G853 ◽  
Author(s):  
Steven D. Lidofsky ◽  
Richard M. Roman
Keyword(s):  
Amino Acid ◽  
Mammalian Cells ◽  
Chloride Channels ◽  
Amino Acid Uptake ◽  
Experimental Models ◽  
Cell Swelling ◽  
Acid Uptake ◽  
Adaptive Responses ◽  
Anion Channels

Cells involved in the retrieval and metabolic conversion of amino acids undergo significant increases in size in response to amino acid uptake. The resultant adaptive responses to cell swelling are thought to include increases in membrane K+ and Cl− permeability through activation of volume-sensitive ion channels. This viewpoint is largely based on experimental models of hypotonic swelling, but few mammalian cells experience hypotonic challenge in vivo. Here we have examined volume regulatory responses in a physiological model of cell-swelling alanine uptake in immortalized hepatocytes. Alanine-induced cell swelling was followed by a decrease in cell volume that was temporally associated with an increase in membrane Cl− currents. These currents were dependent both on alanine concentration and Na+, suggesting that currents were stimulated by Na+-coupled alanine uptake. Cl− currents were outwardly rectifying, exhibited an anion permeability sequence of I− > Br− > Cl−, and were inhibited by the Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid, features similar to those reported for a widely distributed class of volume-sensitive anion channels evoked by experimental hypotonic stress. These findings suggest that volume-sensitive anion channels participate in adaptive responses to amino acid uptake and provide such channels with a new physiological context.

Effects of phenylarsine oxide on insulin-stimulated system A amino acid uptake in skeletal muscle

1991 ◽  
Vol 261 (4) ◽  
pp. C608-C613 ◽  
Author(s):  
E. J. Henriksen
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Isobutyric Acid ◽  
Acid Uptake ◽  
Mammalian Skeletal Muscle ◽  
Phenylarsine Oxide ◽  
System A ◽  
Carrier Molecule ◽  
20 Nm

The role of vicinal sulfhydryls in the stimulation by insulin of system A amino acid uptake in mammalian skeletal muscle was investigated. Neutral amino acid uptake via system A carriers was assessed using the nonmetabolizable analogue alpha-(methylamino)isobutyric acid (MeAIB). Phenylarsine oxide (PAO), a trivalent arsenical that interacts with vicinal sulfhydryls, at 40 microM inhibited basal and insulin-stimulated (2 mU/ml) MeAIB uptake in rat epitrochlearis muscles by approximately 50% and approximately 80%, respectively. No significant changes in the ATP level or in the lactate-to-pyruvate ratio were observed. Both inhibitory effects were completely preventable by coincubation with dimercaptopropanol, a vicinal dithiol, indicating the effects were mediated specifically by interactions with vicinal sulfhydryls. Stimulation of MeAIB uptake by the insulin-mimicker vanadate (10 mM) or by insulin-like growth factor I (IGF-I, 20 nM) was also inhibited by 80-90% by PAO. Kinetic analysis showed that PAO decreased the apparent Vmax for basal and insulin-stimulated MeAIB uptake without altering the apparent Km. MeAIB uptake already maximally stimulated by insulin was rapidly (half-time = approximately 10 min) reversed by the addition of PAO so that the rate of MeAIB uptake was the same as in muscles incubated throughout with insulin and PAO. These results implicate a major role for vicinal sulfhydryls in the stimulation by insulin of amino acid uptake via system A carriers in skeletal muscle and suggest that the site of action of PAO on this system is distal to the insulin receptor, possibly at the carrier molecule itself.

ASC system activity is altered by development of cell polarity in trophoblast from human placenta

1993 ◽  
Vol 265 (1) ◽  
pp. C212-C217 ◽  
Author(s):  
T. C. Furesz ◽  
C. H. Smith ◽  
A. J. Moe
Keyword(s):  
Amino Acid ◽  
Primary Cultures ◽  
Amino Acid Uptake ◽  
Selective Inhibition ◽  
Isobutyric Acid ◽  
Neutral Amino Acid ◽  
Transport Systems ◽  
Bewo Cell ◽  
Acid Uptake

Pathways of neutral amino acid uptake were investigated in vitro during differentiation of primary cultures of trophoblast isolated from full-term human placentas and a clone (b30) of the BeWo cell line. Inhibition of initial alanine (0.1 microM) uptake by 2-(methylamino)isobutyric acid and unlabeled alanine revealed two Na(+)-dependent systems and one Na(+)-independent transporter. Characterization of these transporters, by selective inhibition, suggested system A, ASC, and L-like transporters. Concomitant with formation of microvillous membrane and syncytium, system ASC activity decreased from 16.1 +/- 2.8 pmol.mg DNA-1.min-1 at 24 h to 2.4 +/- 1.1 pmol.mg DNA-1.min-1 at 72 h. Na(+)-independent alanine uptake increased from 6.0 +/- 2.0 to 12.9 +/- 0.9 pmol.mg DNA-1.min-1 at 24 and 72 h, respectively. Similarly, alpha-(methylamino)isobutyric acid-insensitive, Na(+)-dependent activity in b30 cells (100 microM alanine) decreased from 6.5 +/- 1.6 to 1.2 +/- 1.2 nmol.mg DNA-1.min-1 for control and forskolin-treated cells, respectively. We conclude that membrane specialization accompanying fusion and differentiation of the cytotrophoblast to form syncytiotrophoblast results in a polarization of neutral amino acid transport systems.

scholarly journals N-alpha-Aminoacyl Colchicines as Promising Anticancer Agents

2020 ◽  
Vol 17 (1) ◽  
pp. 21-32
Author(s):  
Ana Marzo-Mas ◽  
Laura Conesa-Milián ◽  
Sam Noppen ◽  
Sandra Liekens ◽  
Eva Falomir ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amino Acid ◽  
Anticancer Agents ◽  
Amino Acid Uptake ◽  
In Vivo Studies ◽  
Acid Uptake ◽  
Drug Effectiveness ◽  
M Phase ◽  
Colchicine Derivatives

Background: In the last years, many efforts have been made to find colchicine derivatives with reduced toxicity. Additionally, the deregulation of amino acid uptake by cancer cells provides an opportunity to improve anticancer drug effectiveness. Objective: To design new colchicine derivatives with reduced cytotoxicity and enhanced selectivity by means of introducing aminoacyl groups. Method: 34 colchicine analogues bearing L- and D-amino acid pendants were synthetized and characterized by NMR, IR and MS techniques. Cytotoxicity and antimitotic properties were assessed by spectrophotometry and cell cycle assays. Oncogene downregulation was studied by RTqPCR whereas in vivo studies were performed in SCID mice. Results: Compounds exhibit high antiproliferative activities at the nanomolar level while being, in general, less cytotoxic than colchicine. Most compounds inhibit the polymerization of tubulin in a way similar to colchicine itself, with L-amino acid derivatives being the most active in the inhibition of tubulin polymerization. All selected compounds caused cell cycle arrest at the G2/M phase when tested at 1 μM. More specifically, Boc-L-proline derivative 6 arrested half of the population and showed one of the highest Selectivity Indexes. Derivatives 1 (Boc-glycine), 27 (D-leucine) and 31 (Boc-glycine-glycine) proved fairly active in downregulating the expression of the c-Myc, hTERT and VEGF oncogenes, with compound 6 (Boc-L-proline) having the highest activity. This compound was shown to exert a potent anti-tumor effect when administered intraperitoneally (LD50 > 100 mg/kg for 6, compared with 2.5 mg/kg for colchicine). Conclusion: Compound 6 offers an opportunity to be used in cancer therapy with less toxicity problems than colchicine.

scholarly journals Effects of hormones on protein and amino acid metabolism in mammary-gland explants of mice

1976 ◽  
Vol 158 (2) ◽  
pp. 355-359 ◽  
Author(s):  
L D Anderson ◽  
J A Rillema
Keyword(s):  
Mammary Gland ◽  
Amino Acid ◽  
Protein Biosynthesis ◽  
Insulin Response ◽  
Exposure Period ◽  
Amino Acid Uptake ◽  
Isobutyric Acid ◽  
Leucine Incorporation ◽  
Acid Uptake ◽  
Pregnant Mice

The effects of insulin, cortisol and prolactin on amino acid uptake and protein biosynthesis were determined in mammary-gland explants from mid-pregnant mice. Insulin stimulated [3H]leucine incorporation into protein within 15 min of adding insulin to the incubation medium. Insulin also had a rapid stimulatory effect on the rate of aminoiso[14C]butyric acid uptake, but it had no effect on the intracellular accumulation of [3H]leucine. Cortisol inhibited the rate of [3H]leucine incorporation into protein during the initial 4h of incubation, but it had no effect at subsequent times. [3H]Leucine uptake was unaffected by cortisol, but amino[14C]isobutyric acid uptake was inhibited after a 4h exposure period to this hormone. Prolactin stimulated the rate of [3H]leucine incorporation into protein when tissues were exposed to this hormone for 4h or more; up to 4h, however, no effect of prolactin was detected. At all times tested, prolactin had no effect on the uptake of either amino[14C]isobutyric acid or [3H]leucine. Incubation with actinomycin D abolished the prolactin stimulation of protein biosynthesis, but this antibiotic did not affect the insulin response. A distinct difference in the mechanism of action of these hormones on protein biosynthesis in the mammary gland is thus apparent.

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