Home LiteratureArticle Details
PMID: 6811749 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Amino acid transport in isolated rat hepatocytes.

The Journal of membrane biology ·Vol. 69 ·No. 1 ·1982-00-00 ·Pages 1-12

Kilberg MS

Abstract

Improvements in the collagenase perfusion techniques have made isolated rat hepatocytes a popular model in which to study hepatic function. Our knowledge of hepatic amino acid transport has been advanced as a result of this methodology. Translocation across the hepatocyte plasma membrane can, in some instances, represent the rate-limiting step in the overall metabolism of certain amino acids. Furthermore, regulation of amino acid uptake by hepatocytes appears to play a role in diabetes, and perhaps in malignant transformation. Comparisons between normal adult hepatocytes and several hepatoma cell lines show basic differences in amino acid transport. There are at least eight distinct systems in normal hepatocytes for transport of the hormones. Systems A and N exhibit enhanced uptake rates after the cells have been maintained in the absence of extracellular amino acids, a phenomenon termed adaptive control. Further studies using isolated hepatocytes will increase our basic understanding of membrane transport processes and their regulation.

MeSH Terms
Amino Acids/metabolism Aminoisobutyric Acids/metabolism Animals Biological Transport/drug effects Catecholamines/pharmacology Cell Membrane/metabolism Cells, Cultured Cysteine/metabolism Glucagon/pharmacology Glucocorticoids/pharmacology Glutamine/metabolism Glycine/metabolism Histidine/metabolism In Vitro Techniques Insulin/pharmacology Kinetics Liver/drug effects,metabolism Lysine/metabolism Rats
Chemicals
Amino Acids Aminoisobutyric Acids Catecholamines Glucocorticoids Insulin Glutamine 2-(methylamino)isobutyric acid Histidine Glucagon Lysine Cysteine Glycine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kilberg M S
References (87)
87 references, click to expand
  1. Contrasts in neutral amino acid transport by rabbit erythrocytes and reticulocytes.
    J Biol Chem. 1965 Sep;240(9):3594-600 PMID: 5835941
  2. Comparative studies of alanine and alpha-aminoisobutyric acid uptake by freshly isolated rat liver cells.
    J Biol Chem. 1979 Mar 10;254(5):1653-8 PMID: 762163
  3. Biphasic stimulation of amino acid uptake by glucagon in hepatocytes.
    Biochem Biophys Res Commun. 1980 Sep 16;96(1):61-8 PMID: 7437051
  4. The hormonal control of hepatic gluconeogenesis.
    Recent Prog Horm Res. 1970;26:411-61 PMID: 4319350
  5. Inhibition of amino acid uptake in isolated hepatocytes by selenite.
    FEBS Lett. 1979 Nov 1;107(1):77-80 PMID: 499561
  6. Plasma-membrane transport of alanine is rate-limiting for its metabolism in rat-liver parenchymal cells.
    FEBS Lett. 1980 Oct 6;119(2):271-4 PMID: 7428940
  7. Effects of catecholamines and glucagon on amino acid transport in the liver.
    Endocrinology. 1968 Dec;83(6):1185-92 PMID: 5721992
  8. Regulation of amino acid transport in chick embryo heart cells. I. Adaptive system of mediation for neutral amino acids.
    Biochim Biophys Acta. 1972 May 9;266(2):407-21 PMID: 5038266
  9. Effects of epinephrine on the distribution of two model amino acids in the rat.
    Mol Pharmacol. 1967 Jul;3(4):352-8 PMID: 6040599
  10. Amino acid transport in rat liver and Morris hepatomas: effect of protein diet and hormones on the uptake of alpha-aminoisobutyric acid-14C.
    Cancer Res. 1969 Nov;29(11):2101-15 PMID: 4311566
  11. Effect of glucocorticoids on amino acid transport in isolated rat hepatocytes.
    Mol Cell Endocrinol. 1977 Dec;9(2):205-14 PMID: 598617
  12. Adaptive regulation of amino acid transport in cultured human fibroblasts. Sites and mechanism of action.
    J Biol Chem. 1981 Apr 10;256(7):3191-8 PMID: 7204399
  13. Insulin and glucagon receptors of isolated rat hepatocytes: comparison between hormone binding and amino acid transport stimulation.
    Endocrinology. 1981 Jul;109(1):253-61 PMID: 6263586
  14. Effect of glucagon and dibutyryl cyclic AMP on the tissue distribution of [14-C] alpha-aminoisobutyric acid in rats.
    FEBS Lett. 1975 Apr 15;53(1):8-9 PMID: 166873
  15. Glucocorticoid and catecholamine stimulation of amino acid transport in rat hepatocytes. Synthesis of a high-affinity component.
    Mol Cell Endocrinol. 1980 Sep;19(3):253-61 PMID: 7409305
  16. The glucose-alanine cycle.
    Metabolism. 1973 Feb;22(2):179-207 PMID: 4567003
  17. Amino acid extraction and ammonia metabolism by the human kidney during the prolonged administration of ammonium chloride.
    J Clin Invest. 1963 Feb;42:263-76 PMID: 13940831
  18. Effect of catecholamines on amino acid transport in isolated rat hepatocytes.
    Endocrinology. 1978 Feb;102(2):379-85 PMID: 217591
  19. The regulation of amino acid transport in animal cells.
    Biochim Biophys Acta. 1978 Dec 15;515(4):329-66 PMID: 365236
  20. Cationic amino acid transport into cultured animal cells. II. Transport system barely perceptible in ordinary hepatocytes, but active in hepatoma cell lines.
    J Biol Chem. 1982 Apr 25;257(8):4450-7 PMID: 7068644
  21. The Banting Memorial Lecture 1975. Diabetes and the alpha cell.
    Diabetes. 1976 Feb;25(2):136-51 PMID: 814024
  22. A bicyclic amino acid to improve discriminations among transport systems.
    J Biol Chem. 1969 Mar 25;244(6):1510-20 PMID: 4886308
  23. The significance of differences between fresh cell suspensions and fresh or maintained monolayers.
    Ann N Y Acad Sci. 1980;349:57-66 PMID: 6111977
  24. Amino acid transport in isolated hepatocytes from streptozotocin-diabetic rats.
    Diabetes. 1980 Dec;29(12):996-1000 PMID: 7439542
  25. L-Tryptophan transport in human red blood cells.
    Biochim Biophys Acta. 1980 May 23;598(2):375-84 PMID: 7378409
  26. Muscle and splanchnic glutmine and glutamate metabolism in postabsorptive andstarved man.
    J Clin Invest. 1971 Apr;50(4):814-7 PMID: 5547277
  27. Regulation of amino acid transport systems by amino acid depletion and supplementation in monolayer cultures of rat hepatocytes.
    J Biol Chem. 1978 Dec 25;253(24):9009-17 PMID: 721825
  28. Transport of diamino acids into the Ehrlich cell.
    J Biol Chem. 1966 Dec 10;241(23):5542-51 PMID: 5951602
  29. Cysteine as a system-specific substrate for transport system ASC in rat hepatocytes.
    Biochem Biophys Res Commun. 1979 May 28;88(2):744-51 PMID: 465067
  30. The use of N-methylation to direct route of mediated transport of amino acids.
    J Biol Chem. 1965 Sep;240(9):3609-16 PMID: 5891075
  31. Alpha- and beta-cell interrelationships in health and disease.
    Metabolism. 1974 Jun;23(6):581-93 PMID: 4597501
  32. Na plus-facilitated reactions of neutral amino acids with a cationic amino acid transport system.
    Proc Natl Acad Sci U S A. 1969 Jul;63(3):948-55 PMID: 5259774
  33. Inductions by hormones added singly, simultaneously or sequentially: what cultured hepatocytes can tell us about metabolic regulation in the whole animal.
    Adv Enzyme Regul. 1976;14:103-15 PMID: 9786
  34. Characteristics of an amino acid transport system in rat liver for glutamine, asparagine, histidine, and closely related analogs.
    J Biol Chem. 1980 May 10;255(9):4011-9 PMID: 7372663
  35. Transport systems for neutral amino acids in the pigeon erythrocyte.
    J Biol Chem. 1967 Nov 25;242(22):5386-96 PMID: 6065101
  36. 3':5'-cyclic AMP: independent induction of amino acid transport by epinephrine in primary cultures of adult rat liver cells.
    Proc Natl Acad Sci U S A. 1977 Jan;74(1):234-7 PMID: 13365
  37. A distinct Na+-requiring transport system for alanine, serine, cysteine, and similar amino acids.
    J Biol Chem. 1967 Nov 25;242(22):5237-46 PMID: 6070848
  38. Microfilament accumulation and the transport of amino acids and glucose in adult rat hepatocytes cultured on collagen gel/nylon mesh.
    Biochem Biophys Res Commun. 1981 Jan 15;98(1):203-10 PMID: 7213384
  39. Effects of glucagon on amino acid transport and utilization in the perfused rat liver.
    J Biol Chem. 1969 Oct 25;244(20):5724-8 PMID: 4310605
  40. Repression, derepression, transinhibition, and trans-stimulation of amino acid transport in rat hepatocytes and four rat hepatoma cell lines in culture.
    J Biol Chem. 1979 Jul 25;254(14):6691-7 PMID: 447744
  41. Induction of amino acid transport in primary cultures of adult rat liver parenchymal cells by insulin.
    J Biol Chem. 1976 May 25;251(10):3014-20 PMID: 1270436
  42. The transport of branched-chain amino acids into isolated rat liver cells.
    FEBS Lett. 1977 Aug 15;80(2):380-4 PMID: 891989
  43. Endocrine control of amino acid transfer; distribution of an unmetabolizable amino acid.
    Science. 1957 Nov 15;126(3281):1002-5 PMID: 13486048
  44. Transport of amino acids into the oestrogen-primed uterus. Enchancement of the uptake by a preliminary incubation.
    Biochem J. 1972 Jun;128(1):19-27 PMID: 5085566
  45. Modulation of amino acid transport in rat liver slices by tissue preincubation.
    Z Naturforsch C. 1980 Nov-Dec;35(11-12):1019-23 PMID: 6163260
  46. Glucagon stimulates the A system for neutral amino acid transport in isolated hepatocytes of adult rat.
    Biochem Biophys Res Commun. 1976 Oct 4;72(3):893-901 PMID: 186064
  47. Hormonal regulation of membrane phenotype in hepatoma cells.
    Ann N Y Acad Sci. 1980;349:210-20 PMID: 6261629
  48. Glucocorticoid inhibition of two discrete glycine transport systems in rat hepatoma cells.
    J Biol Chem. 1980 Jun 25;255(12):5708-14 PMID: 7380834
  49. Effect of hydrocortisone and insulin on uptake of alpha-aminoisobutyric acid by isolated perfused rat liver.
    Mol Pharmacol. 1965 Jul;1(1):66-76 PMID: 5835080
  50. A "permissive" effect of dexamethasone on the glucagon induction of amino acid transport in cultured hepatocytes.
    Nature. 1975 Jul 3;256(5512):46-7 PMID: 166322
  51. Incomplete correspondence between repressive and substrate action by amino acids on transport systems A and N in monolayered rat hepatocytes.
    J Biol Chem. 1982 Jan 10;257(1):345-8 PMID: 7053375
  52. Hormonal regulation of amino acid transport and gluconeogenesis in primary cultures of adult rat liver parenchymal cells.
    J Cell Physiol. 1976 Dec;89(4):641-6 PMID: 188835
  53. Calcium-dependent hormonal regulation of amino acid transport and cyclic AMP accumulation in rat hepatocyte monolayer cultures.
    Proc Natl Acad Sci U S A. 1980 Oct;77(10):5953-7 PMID: 6255469
  54. Permissive effect of dexamethasone on glucagon induction of urea-cycle enzymes in perifused primary monolayer cultures of rat hepatocytes.
    Eur J Biochem. 1979 Jun;97(1):29-35 PMID: 477671
  55. Effect of insulin on amino acid transport in isolated rat hepatocytes.
    Diabetologia. 1978 Aug;15(2):117-23 PMID: 700271
  56. Characteristics of system ASC for transport of neutral amino acids in the isolated rat hepatocyte.
    J Biol Chem. 1981 Apr 10;256(7):3304-12 PMID: 7204404
  57. Anion effects on glycine entry into pigeon red blood cells.
    Biochim Biophys Acta. 1972 Oct 23;288(1):153-65 PMID: 4640384
  58. Effect of insulin, dexamethasone, and glucagon on the amino acid transport ability of four rat hepatoma cell lines and rat hepatocytes in culture.
    Cancer Res. 1978 Dec;38(12):4591-600 PMID: 214227
  59. Surprising differences in substrate selectivity and other properties of systems A and ASC between rat hepatocytes and the hepatoma cell line HTC.
    J Biol Chem. 1981 Aug 10;256(15):7905-9 PMID: 6790528
  60. Na+/Li+ selectivity in transport system A: effects of substrate structure.
    J Membr Biol. 1977 Dec 15;37(3-4):193-211 PMID: 563921
  61. Stringent control in E. coli.
    Annu Rev Genet. 1979;13:393-415 PMID: 94252
  62. Role of microtubules in insulin and glucagon stimulation of amino acid transport in isolated rat hepatocytes.
    J Biol Chem. 1981 May 10;256(9):4336-40 PMID: 6260794
  63. Amino acid metabolism in exercising man.
    J Clin Invest. 1971 Dec;50(12):2703-14 PMID: 5129318
  64. Decreased uptake of 14C-labeled dicarboxylic amino acids in rapidly growing hepatomas.
    Cancer Res. 1980 Nov;40(11):4053-8 PMID: 7471051
  65. DISTINCT MEDIATING SYSTEMS FOR THE TRANSPORT OF NEUTRAL AMINO ACIDS BY THE EHRLICH CELL.
    J Biol Chem. 1963 Nov;238:3686-99 PMID: 14109206
  66. Adaptive regulation of amino acid transport across the cell membrane in avian and mammalian tissues.
    Biochim Biophys Acta. 1975 Oct 6;406(2):264-79 PMID: 1238115
  67. Stimulation of alanine transport and metabolism by dibutyryl cyclic AMP in the hepatocytes from fed rats. Assessment of transport as a potential rate-limiting step for alanine metabolism.
    Biochim Biophys Acta. 1981 Jun 22;644(2):295-304 PMID: 6266469
  68. Stimulation of amino acid transport in rat liver slices by epinephrine, glucagon, and adenosine 3',5'-monophosphate.
    J Biol Chem. 1970 Jun 10;245(11):3026-32 PMID: 4317880
  69. Role of protein dissociation in the transport of acidic amino acids by the Ehrlich ascites tumor cell.
    Biochim Biophys Acta. 1977 Jan 21;464(2):295-312 PMID: 12815
  70. Gluconeogenesis in rat liver parenchymal cells in primary culture: permissive effect of the glucocorticoids on glucagon stimulation of gluconeogenesis.
    J Cell Physiol. 1981 Apr;107(1):11-9 PMID: 7217222
  71. Insulin and glucagon stimulation of amino acid transport in isolated rat hepatocytes. Synthesis of a high affinity component of transport.
    J Biol Chem. 1979 Oct 25;254(20):10431-7 PMID: 489605
  72. Hormonal regulation of hepatic amino acid transport.
    J Supramol Struct. 1977;6(2):191-204 PMID: 198613
  73. Binding of 125I-labeled glucagon and glucagon-stimulated accumulation of adenosine 3':5'-monophosphate in isolated intact rat hepatocytes. Evidence for receptor heterogeneity.
    J Biol Chem. 1978 May 10;253(9):3203-10 PMID: 205543
  74. Growth hormone stimulation of amino acid transport and utilization by the perfused rat liver.
    J Biol Chem. 1975 Jan 10;250(1):197-204 PMID: 1141204
  75. Neutral amino acid transport systems in Chinese hamster ovary cells.
    J Biol Chem. 1981 Jun 10;256(11):5422-7 PMID: 7240147
  76. Aminoisobutyric acid transport in primary cultures of normal adult rat hepatocytes.
    Proc Soc Exp Biol Med. 1975 Sep;149(4):1019-22 PMID: 1166067
  77. Characteristics of the transport of alanine, serine and glutamine across the plasma membrane of isolated rat liver cells.
    Biochem J. 1978 Dec 15;176(3):827-36 PMID: 747655
  78. Insulin stimulation of amino acid transport in isolated rat hepatocytes is independent of hormone internalization.
    Biochem Biophys Res Commun. 1979 Jun 13;88(3):873-81 PMID: 223575
  79. Role of system Gly in glycine transport in monolayer cultures of liver cells.
    Biochem Biophys Res Commun. 1981 Jan 15;98(1):102-7 PMID: 6163428
  80. Heterogeneity of Na+-independent 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid and L-leucine transport in isolated rat hepatocytes in primary culture.
    Biochem Biophys Res Commun. 1982 Jan 15;104(1):307-13 PMID: 7073676
  81. Induction and decay of glucagon-induced amino acid transport in primary cultures of adult rat liver cells: paradoxical effects of cycloheximide and puromycin.
    Proc Natl Acad Sci U S A. 1976 Dec;73(12):4511-5 PMID: 188042
  82. Amino acid concentration by a free cell neoplasm; relations among amino acids.
    J Biol Chem. 1952 Sep;198(1):1-15 PMID: 12999712
  83. A stereoselective anomaly in dicarboxylic amino acid transport.
    J Biol Chem. 1981 Jun 25;256(12):6054-9 PMID: 6113243
  84. Hormonal regulation of amino acid transport and cAMP production in monolayer cultures of rat hepatocytes.
    J Cell Physiol. 1980 Apr;103(1):159-68 PMID: 6253504
  85. Muscle alanine synthesis and hepatic gluconeogenesis.
    Biochem Soc Trans. 1980 Apr;8(2):205-13 PMID: 6989679
  86. Evidence for a hepatic transport system not responsive to glucagon or theophylline.
    Biochem Biophys Res Commun. 1971 Apr 2;43(1):119-25 PMID: 5579936
  87. Antagonistic effect of insulin on glucagon-evoked hyperpolarization. A correlation between changes in membrane potential and gluconeogenesis.
    Biochim Biophys Acta. 1980 Feb 28;596(2):180-5 PMID: 6986911
Article Info
Journal
The Journal of membrane biology
Abbr.
J Membr Biol
ISSN
0022-2631
Published
1982-00-00
Pages
1-12
Language
English
Region
United States
NLM ID
0211301
Subset
IM
Grants
NIADDK NIH HHS · AM-28374 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com