Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Nov 1;271(3):575–583. doi: 10.1042/bj2710575

Stimulation of apolipoprotein secretion in very-low-density and high-density lipoproteins from cultured rat hepatocytes by dexamethasone.

P Martin-Sanz 1, J E Vance 1, D N Brindley 1
PMCID: PMC1149601  PMID: 2244866

Abstract

The effects of dexamethasone (a synthetic glucocorticoid) and insulin on the secretion of very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) were investigated. Rat hepatocytes in monolayer culture were preincubated for 15 h in the presence or absence of combinations of 100 nM-dexamethasone and 2 nM-, 10 nM- or 50 nM-insulin. Dexamethasone increased [3H]oleate incorporation into secreted triacylglycerol by 2.7-fold and the mass of triacylglycerol secreted by 1.5-fold. Insulin alone decreased these parameters and antagonized the effect of dexamethasone. Dexamethasone increased the secretion of [3H]leucine in apolipoprotein (apo) E, and in the large (BH) and small (BI) forms of apo B in VLDL by about 7.1-, 3.6- and 4.0-fold respectively. Insulin alone decreased the secretion of these 3H-labelled apolipoproteins in VLDL. However, 2 nM-insulin with dexamethasone increased the secretion of 3H-labelled apo BH and apo BL by a further 0.8- and 3.2-fold respectively; 50 nM-insulin decreased the secretions of apo E, apo BH and apo BL in VLDL. Similar effects for dexamethasone or insulin alone were also obtained for the masses of apo E and apo BL + H secreted in VLDL. Albumin secretion was not significantly altered by either dexamethasone or insulin alone, but in combination they stimulated by 2.1-2.6-fold. Insulin or dexamethasone alone had little effect on the secretion of apolipoproteins in the HDL fraction. However, dexamethasone plus 2 nM-insulin increased the incorporation of [3H]leucine into apo AI, apo AH plus apo C, apo AIV and apo E of HDL by about 1.8-, 1.6-, 1.7- and 2.0-fold respectively. The apo E in the bottom fraction represented about 69% of the total 3H-labelled apo E secreted. The responses in the total secretion of apo E from the hepatocytes resembled those seen in HDL. The interactions of insulin and dexamethasone are discussed in relation to the general regulation of lipoprotein metabolism, the development of hyperlipidaemias and the predisposition to premature atherosclerosis.

Full text

PDF
579

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alcindor L. G., Infante R., Soler-Argilaga C., Polonovski J. Effect of a single insulin administration on the hepatic release of triglycerides into the plasma. Biochim Biophys Acta. 1973 Jun 21;306(3):347–352. doi: 10.1016/0005-2760(73)90173-2. [DOI] [PubMed] [Google Scholar]
  2. Amatruda J. M., Danahy S. A., Chang C. L. The effects of glucocorticoids on insulin-stimulated lipogenesis in primary cultures of rat hepatocytes. Biochem J. 1983 Apr 15;212(1):135–141. doi: 10.1042/bj2120135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashby P., Robinson D. S. Effects of insulin, glucocorticoids and adrenaline on the activity of rat adipose-tissue lipoprotein lipids. Biochem J. 1980 Apr 15;188(1):185–192. doi: 10.1042/bj1880185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. Bartlett S. M., Gibbons G. F. Short- and longer-term regulation of very-low-density lipoprotein secretion by insulin, dexamethasone and lipogenic substrates in cultured hepatocytes. A biphasic effect of insulin. Biochem J. 1988 Jan 1;249(1):37–43. doi: 10.1042/bj2490037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beynen A. C., Geelen M. J. Short-term regulation of hepatic triacylglycerol metabolism by insulin and glucagon. Vet Res Commun. 1982 May;5(3):223–236. doi: 10.1007/BF02214989. [DOI] [PubMed] [Google Scholar]
  7. Brindle N. P., Ontko J. A. Alpha-adrenergic suppression of very-low-density-lipoprotein triacylglycerol secretion by isolated rat hepatocytes. Biochem J. 1988 Mar 1;250(2):363–368. doi: 10.1042/bj2500363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brindley D. N., Brown N. F., Salter A. M., Fisher S. C., Fears R. Role of insulin and counter-regulatory hormones in the control of hepatic glycerolipid synthesis and low-density-lipoprotein catabolism in diabetes. Biochem Soc Trans. 1989 Feb;17(1):43–46. doi: 10.1042/bst0170043. [DOI] [PubMed] [Google Scholar]
  9. Brindley D. N., Rolland Y. Possible connections between stress, diabetes, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis. Clin Sci (Lond) 1989 Nov;77(5):453–461. doi: 10.1042/cs0770453. [DOI] [PubMed] [Google Scholar]
  10. Cascales C., Mangiapane E. H., Brindley D. N. Oleic acid promotes the activation and translocation of phosphatidate phosphohydrolase from the cytosol to particulate fractions of isolated rat hepatocytes. Biochem J. 1984 May 1;219(3):911–916. doi: 10.1042/bj2190911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cole T. G., Wilcox H. G., Heimberg M. Effects of adrenalectomy and dexamethasone on hepatic lipid metabolism. J Lipid Res. 1982 Jan;23(1):81–91. [PubMed] [Google Scholar]
  12. Crane L. J., Miller D. L. Plasma protein synthesis by isolated rat hepatocytes. J Cell Biol. 1977 Jan;72(1):11–25. doi: 10.1083/jcb.72.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davis R. A., Dluz S. M., Leighton J. K., Brengaze V. A. Increased translatable mRNA and decreased lipogenesis are responsible for the augmented secretion of lipid-deficient apolipoprotein E by hepatocytes from fasted rats. J Biol Chem. 1989 May 25;264(15):8970–8977. [PubMed] [Google Scholar]
  14. Davis R. A., Prewett A. B., Chan D. C., Thompson J. J., Borchardt R. A., Gallaher W. R. Intrahepatic assembly of very low density lipoproteins: immunologic characterization of apolipoprotein B in lipoproteins and hepatic membrane fractions and its intracellular distribution. J Lipid Res. 1989 Aug;30(8):1185–1196. [PubMed] [Google Scholar]
  15. Diamant S., Shafrir E. Modulation of the activity of insulin-dependent enzymes of lipogenesis by glucocorticoids. Eur J Biochem. 1975 May 6;53(2):541–546. doi: 10.1111/j.1432-1033.1975.tb04097.x. [DOI] [PubMed] [Google Scholar]
  16. Duerden J. M., Bartlett S. M., Gibbons G. F. Long-term maintenance of high rates of very-low-density-lipoprotein secretion in hepatocyte cultures. A model for studying the direct effects of insulin and insulin deficiency in vitro. Biochem J. 1989 Nov 1;263(3):937–943. doi: 10.1042/bj2630937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Duerden J. M., Bartlett S. M., Gibbons G. F. Regulation of very-low-density-lipoprotein lipid secretion in hepatocyte cultures derived from diabetic animals. Biochem J. 1989 Aug 15;262(1):313–319. doi: 10.1042/bj2620313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Durrington P. N., Newton R. S., Weinstein D. B., Steinberg D. Effects of insulin and glucose on very low density lipoprotein triglyceride secretion by cultured rat hepatocytes. J Clin Invest. 1982 Jul;70(1):63–73. doi: 10.1172/JCI110604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Elovson J., Chatterton J. E., Bell G. T., Schumaker V. N., Reuben M. A., Puppione D. L., Reeve J. R., Jr, Young N. L. Plasma very low density lipoproteins contain a single molecule of apolipoprotein B. J Lipid Res. 1988 Nov;29(11):1461–1473. [PubMed] [Google Scholar]
  20. Elshourbagy N. A., Boguski M. S., Liao W. S., Jefferson L. S., Gordon J. I., Taylor J. M. Expression of rat apolipoprotein A-IV and A-I genes: mRNA induction during development and in response to glucocorticoids and insulin. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8242–8246. doi: 10.1073/pnas.82.23.8242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Follenius M., Brandenberger G., Hietter B. Diurnal cortisol peaks and their relationships to meals. J Clin Endocrinol Metab. 1982 Oct;55(4):757–761. doi: 10.1210/jcem-55-4-757. [DOI] [PubMed] [Google Scholar]
  22. Gibbons G. F. Insulin, diabetes and hepatic very-low-density lipoprotein metabolism. Biochem Soc Trans. 1989 Feb;17(1):49–51. doi: 10.1042/bst0170049. [DOI] [PubMed] [Google Scholar]
  23. Gibbons G. F., Pullinger C. R. Regulation of hepatic very-low-density lipoprotein secretion in rats fed on a diet high in unsaturated fat. Biochem J. 1987 Apr 15;243(2):487–492. doi: 10.1042/bj2430487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Graham A., Bennett A. J., McLean A. A., Zammit V. A., Brindley D. N. Factors regulating the secretion of lysophosphatidylcholine by rat hepatocytes compared with the synthesis and secretion of phosphatidylcholine and triacylglycerol. Effects of albumin, cycloheximide, verapamil, EGTA and chlorpromazine. Biochem J. 1988 Aug 1;253(3):687–692. doi: 10.1042/bj2530687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Haagsman H. P., van Golde L. M. Regulation of hepatic triacylglycerol synthesis and secretion. Vet Res Commun. 1984 Aug;8(3):157–171. doi: 10.1007/BF02214708. [DOI] [PubMed] [Google Scholar]
  26. Hamilton R. L., Guo L. S., Felker T. E., Chao Y. S., Havel R. J. Nascent high density lipoproteins from liver perfusates of orotic acid-fed rats. J Lipid Res. 1986 Sep;27(9):967–978. [PubMed] [Google Scholar]
  27. Ide T., Ontko J. A. Increased secretion of very low density lipoprotein triglyceride following inhibition of long chain fatty acid oxidation in isolated rat liver. J Biol Chem. 1981 Oct 25;256(20):10247–10255. [PubMed] [Google Scholar]
  28. Jennings R. J., Lawson N., Fears R., Brindley D. N. Stimulation of the activities of phosphatidate phosphohydrolase and tyrosine aminotransferase in rat hepatocytes by glucocorticoids. FEBS Lett. 1981 Oct 12;133(1):119–122. doi: 10.1016/0014-5793(81)80485-1. [DOI] [PubMed] [Google Scholar]
  29. Kempen H. J. Lipoprotein secretion by isolated rat hepatocytes: characterization of the lipid-carrying particles and modulation of their release. J Lipid Res. 1980 Aug;21(6):671–680. [PubMed] [Google Scholar]
  30. Kim M. H., Nakayama R., Manos P., Tomlinson J. E., Choi E., Ng J. D., Holten D. Regulation of apolipoprotein E synthesis and mRNA by diet and hormones. J Lipid Res. 1989 May;30(5):663–671. [PubMed] [Google Scholar]
  31. Kirk C. J., Verrinder T. R., Hems D. A. Fatty acid synthesis in the perfused liver of adrenalectomized rats. Biochem J. 1976 Jun 15;156(3):593–602. doi: 10.1042/bj1560593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Klausner H., Heimberg M. Effect of adrenalcortical hormones on release of triglycerides and glucose by liver. Am J Physiol. 1967 Jun;212(6):1236–1246. doi: 10.1152/ajplegacy.1967.212.6.1236. [DOI] [PubMed] [Google Scholar]
  33. Knox A. M., Sturton R. G., Cooling J., Brindley D. N. Control of hepatic triacylglycerol synthesis. Diurnal variations in hepatic phosphatidate phosphohydrolase activity and in the concentrations of circulating insulin and corticosterone in rats. Biochem J. 1979 May 15;180(2):441–443. doi: 10.1042/bj1800441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Krausz Y., Bar-On H., Shafrir E. Origin and pattern of glucocorticoid-induced hyperlipidemia in rats. Dose-dependent bimodal changes in serum lipids and lipoproteins in relation to hepatic lipogenesis and tissue lipoprotein lipase activity. Biochim Biophys Acta. 1981 Jan 26;663(1):69–82. doi: 10.1016/0005-2760(81)90195-8. [DOI] [PubMed] [Google Scholar]
  35. Krul E. S., Dolphin P. J., Rubinstein D. Secretion of nascent lipoproteins by isolated rat hepatocytes. Can J Biochem. 1981 Aug;59(8):676–686. doi: 10.1139/o81-094. [DOI] [PubMed] [Google Scholar]
  36. Laker M. E., Mayes P. A. Investigations into the direct effects of insulin on hepatic ketogenesis, lipoprotein secretion and pyruvate dehydrogenase activity. Biochim Biophys Acta. 1984 Sep 12;795(2):427–430. doi: 10.1016/0005-2760(84)90094-8. [DOI] [PubMed] [Google Scholar]
  37. Lin R. C. Effects of hormones on apolipoprotein secretion in cultured rat hepatocytes. Metabolism. 1988 Aug;37(8):745–751. doi: 10.1016/0026-0495(88)90009-1. [DOI] [PubMed] [Google Scholar]
  38. Luo M., Vriend G., Kamer G., Minor I., Arnold E., Rossmann M. G., Boege U., Scraba D. G., Duke G. M., Palmenberg A. C. The atomic structure of Mengo virus at 3.0 A resolution. Science. 1987 Jan 9;235(4785):182–191. doi: 10.1126/science.3026048. [DOI] [PubMed] [Google Scholar]
  39. Mangeney M., Cardot P., Lyonnet S., Coupe C., Benarous R., Munnich A., Girard J., Chambaz J., Bereziat G. Apolipoprotein-E-gene expression in rat liver during development in relation to insulin and glucagon. Eur J Biochem. 1989 Apr 15;181(1):225–230. doi: 10.1111/j.1432-1033.1989.tb14715.x. [DOI] [PubMed] [Google Scholar]
  40. Mangiapane E. H., Brindley D. N. Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes. Biochem J. 1986 Jan 1;233(1):151–160. doi: 10.1042/bj2330151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Masumoto A., Koga S., Uchida E., Ibayashi H. Effects of insulin, dexamethasone and glucagon on the production of apolipoprotein A-I in cultured rat hepatocytes. Atherosclerosis. 1988 Apr;70(3):217–223. doi: 10.1016/0021-9150(88)90172-4. [DOI] [PubMed] [Google Scholar]
  42. Minshull M., Strong C. R. The stimulation of lipogenesis in white adipose tissue from fed rats by corticosterone. Int J Biochem. 1985;17(4):529–532. doi: 10.1016/0020-711x(85)90151-x. [DOI] [PubMed] [Google Scholar]
  43. Oschry Y., Eisenberg S. Rat plasma lipoproteins: re-evaluation of a lipoprotein system in an animal devoid of cholesteryl ester transfer activity. J Lipid Res. 1982 Nov;23(8):1099–1106. [PubMed] [Google Scholar]
  44. Patsch W., Franz S., Schonfeld G. Role of insulin in lipoprotein secretion by cultured rat hepatocytes. J Clin Invest. 1983 May;71(5):1161–1174. doi: 10.1172/JCI110865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Penhos J. C., Wu C. H., Lemberg A., Daunas J., Brodoff B., Sodero A., Levine R. The effect of insulin on the metabolism of lipids and on urea formation by the perfused rat liver. Metabolism. 1968 Mar;17(3):246–259. doi: 10.1016/0026-0495(68)90127-3. [DOI] [PubMed] [Google Scholar]
  46. Pietri A. O., Dunn F. L., Grundy S. M., Raskin P. The effect of continuous subcutaneous insulin infusion on very-low-density lipoprotein triglyceride metabolism in type I diabetes mellitus. Diabetes. 1983 Jan;32(1):75–81. doi: 10.2337/diab.32.1.75. [DOI] [PubMed] [Google Scholar]
  47. Pittner R. A., Fears R., Brindley D. N. Effects of insulin, glucagon, dexamethasone, cyclic GMP and spermine on the stability of phosphatidate phosphohydrolase activity in cultured rat hepatocytes. Biochem J. 1986 Nov 15;240(1):253–257. doi: 10.1042/bj2400253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pittner R. A., Fears R., Brindley D. N. Interactions of insulin, glucagon and dexamethasone in controlling the activity of glycerol phosphate acyltransferase and the activity and subcellular distribution of phosphatidate phosphohydrolase in cultured rat hepatocytes. Biochem J. 1985 Sep 1;230(2):525–534. doi: 10.1042/bj2300525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Pullinger C. R., Gibbons G. F. Effects of hormones and pyruvate on the rates of secretion of very-low-density lipoprotein triacylglycerol and cholesterol by rat hepatocytes. Biochim Biophys Acta. 1985 Jan 9;833(1):44–51. doi: 10.1016/0005-2760(85)90251-6. [DOI] [PubMed] [Google Scholar]
  50. Pullinger C. R., North J. D., Teng B. B., Rifici V. A., Ronhild de Brito A. E., Scott J. The apolipoprotein B gene is constitutively expressed in HepG2 cells: regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half-life. J Lipid Res. 1989 Jul;30(7):1065–1077. [PubMed] [Google Scholar]
  51. Quigley M. E., Yen S. S. A mid-day surge in cortisol levels. J Clin Endocrinol Metab. 1979 Dec;49(6):945–947. doi: 10.1210/jcem-49-6-945. [DOI] [PubMed] [Google Scholar]
  52. Reaven E. P., Kolterman O. G., Reaven G. M. Ultrastructural and physiological evidence for corticosteroid-induced alterations in hepatic production of very low density lipoprotein particles. J Lipid Res. 1974 Jan;15(1):74–83. [PubMed] [Google Scholar]
  53. Salter A. M., Fisher S. C., Brindley D. N. Binding of low-density lipoprotein to monolayer cultures of rat hepatocytes is increased by insulin and decreased by dexamethasone. FEBS Lett. 1987 Aug 10;220(1):159–162. doi: 10.1016/0014-5793(87)80895-5. [DOI] [PubMed] [Google Scholar]
  54. Salter A. M., Fisher S. C., Brindley D. N. Interactions of triiodothyronine, insulin and dexamethasone on the binding of human LDL to rat hepatocytes in monolayer culture. Atherosclerosis. 1988 May;71(1):77–80. doi: 10.1016/0021-9150(88)90304-8. [DOI] [PubMed] [Google Scholar]
  55. Slag M. F., Ahmad M., Gannon M. C., Nuttall F. Q. Meal stimulation of cortisol secretion: a protein induced effect. Metabolism. 1981 Nov;30(11):1104–1108. doi: 10.1016/0026-0495(81)90055-x. [DOI] [PubMed] [Google Scholar]
  56. Sleder J., Chen Y. D., Cully M. D., Reaven G. M. Hyperinsulinemia in fructose-induced hypertriglyceridemia in the rat. Metabolism. 1980 Apr;29(4):303–305. doi: 10.1016/0026-0495(80)90001-3. [DOI] [PubMed] [Google Scholar]
  57. Sparks C. E., Sparks J. D., Bolognino M., Salhanick A., Strumph P. S., Amatruda J. M. Insulin effects on apolipoprotein B lipoprotein synthesis and secretion by primary cultures of rat hepatocytes. Metabolism. 1986 Dec;35(12):1128–1136. doi: 10.1016/0026-0495(86)90026-0. [DOI] [PubMed] [Google Scholar]
  58. Sparks J. D., Sparks C. E., Miller L. L. Insulin effects on apolipoprotein B production by normal, diabetic and treated-diabetic rat liver and cultured rat hepatocytes. Biochem J. 1989 Jul 1;261(1):83–88. doi: 10.1042/bj2610083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Strobl W., Gorder N. L., Fienup G. A., Lin-Lee Y. C., Gotto A. M., Jr, Patsch W. Effect of sucrose diet on apolipoprotein biosynthesis in rat liver. Increase in apolipoprotein E gene transcription. J Biol Chem. 1989 Jan 15;264(2):1190–1194. [PubMed] [Google Scholar]
  60. Taskinen M. R., Nikkilä E. A., Pelkonen R., Sane T. Plasma lipoproteins, lipolytic enzymes, and very low density lipoprotein triglyceride turnover in Cushing's syndrome. J Clin Endocrinol Metab. 1983 Sep;57(3):619–626. doi: 10.1210/jcem-57-3-619. [DOI] [PubMed] [Google Scholar]
  61. Tobey T. A., Greenfield M., Kraemer F., Reaven G. M. Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics, and plasma triglyceride levels in normotriglyceridemic man. Metabolism. 1981 Feb;30(2):165–171. doi: 10.1016/0026-0495(81)90167-0. [DOI] [PubMed] [Google Scholar]
  62. Topping D. L., Mayes P. A. The immediate effects of insulin and fructose on the metabolism of the perfused liver. Changes in lipoprotein secretion, fatty acid oxidation and esterification, lipogenesis and carbohydrate metabolism. Biochem J. 1972 Jan;126(2):295–311. doi: 10.1042/bj1260295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Vance D. E., Weinstein D. B., Steinberg D. Isolation and analysis of lipoproteins secreted by rat liver hepatocytes. Biochim Biophys Acta. 1984 Jan 17;792(1):39–47. doi: 10.1016/0005-2760(84)90280-7. [DOI] [PubMed] [Google Scholar]
  64. Vogelberg K. H., Gries F. A., Moschinski D. Hepatic production of VLDL-triglycerides. Dependence of portal substrate and insulin concentration. Horm Metab Res. 1980 Dec;12(12):688–694. doi: 10.1055/s-2007-999233. [DOI] [PubMed] [Google Scholar]
  65. Whitton P. D., Hems D. A. Glycogen synthesis in the perfused liver of adrenalectomized rats. Biochem J. 1976 Jun 15;156(3):585–592. doi: 10.1042/bj1560585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Woodside W. F., Heimberg M. Effects of anti-insulin serum, insulin, and glucose on output of triglycerides and on ketogenesis by the perfused rat liver. J Biol Chem. 1976 Jan 10;251(1):13–23. [PubMed] [Google Scholar]
  67. Yao Z. M., Vance D. E. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J Biol Chem. 1988 Feb 25;263(6):2998–3004. [PubMed] [Google Scholar]
  68. Yudkin J., Szanto S. Hyperinsulinism and atherogenesis. Br Med J. 1971 Feb 6;1(5744):349–349. doi: 10.1136/bmj.1.5744.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. al-Sieni A. I., Plested C. P., Rolland Y., Brindley D. N. Decreased incorporation of glucose into lipids and increased lactate production by adipose tissue after long-term treatment of rats with D-fenfluramine. Biochem Pharmacol. 1989 Nov 1;38(21):3661–3667. doi: 10.1016/0006-2952(89)90569-8. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES