Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1977 Jan 15;162(1):1–8. doi: 10.1042/bj1620001

Effects of prostaglandin on substrate uptake and cell division in human diploid fibroblasts.

P Polgar, L Taylor
PMCID: PMC1164562  PMID: 192204

Abstract

PG (prostaglandin) E1 inhibits the uptake of iridine, thymidine, 2-deoxy-D-glucose and L-isoleucine into human diploid WI38 fibroblasts. The inhibition occurs within seconds of the addition of the prostaglandin to the culture. PGE2, PGF1alpha and PGF2alpha behave similarly. Arachidonic acid and 8,11,14-eicosatrienoic acid also decrease uptake in the presence or absence of indomethacin. Other unsaturated fatty acids such as oleic acid, linoleic acid and linolenic acid are essentially inactive. Ricinoleic acid (the 9-hydroxyoleic acid), however, inhibits uptake to about the same degree, at concentrations similar to those of the prostaglandins. Results indicate that this rapid blockage by the prostaglandins and certain fatty acids is not cyclic AMP-mediated. For example, although PGF1alpha and PGF2alpha are much poorer stimulators of cyclic AMP formation than are PGE1 and PGE2, they are nevertheless effective inhibitors of substrate uptake. Adrenaline, a very effective stimulator of cyclic AMP formation in the cells, is not inhibitory. Also, the addition of 8-methylthioadenosine 3':5'-cyclic monophosphate (methylthio cyclic AMP) to the culture, methylthio cyclic AMP decreases the uptake of nucleotides into cultures undergoing active cell division, approximately to values found in quiescent cultures. PGE1 also has this effect on cells undergoing active growth. This gradual decrease is substrate uptake caused by PGE1 appears to be a separate event from its initial rapid inhibition of uptake.

Full text

PDF
1

Selected References

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

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Costlow M., Baserga R. Changes in membrane transport function in G0 and G1 cells. J Cell Physiol. 1973 Dec;82(3):411–419. doi: 10.1002/jcp.1040820311. [DOI] [PubMed] [Google Scholar]
  3. Cunningham D. D., Pardee A. B. Transport changes rapidly initiated by serum addition to "contact inhibited" 3T3 cells. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1049–1056. doi: 10.1073/pnas.64.3.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Froehlich J. E., Rachmeler M. Effect of adenosine 3'-5'-cyclic monophosphate on cell proliferation. J Cell Biol. 1972 Oct;55(1):19–31. doi: 10.1083/jcb.55.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grimes W. J., Schroeder J. L. Dibutyryl cyclic adenosine 3'5' monophosphate, sugar transport, and regulatory control of cell division in normal and transformed cells. J Cell Biol. 1973 Feb;56(2):487–491. doi: 10.1083/jcb.56.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hauschka P. V., Everhart L. P., Rubin R. W. Alteration of nucleoside transport of Chinese hamster cells by dibutyryl adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3542–3546. doi: 10.1073/pnas.69.12.3542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Johnson M., Ramwell P. W. Prostaglandin modification of membrane-bound enzyme activity: a possible mechanism of action? Prostaglandins. 1973 May;3(5):703–719. doi: 10.1016/0090-6980(73)90106-8. [DOI] [PubMed] [Google Scholar]
  8. Kelly L. A., Butcher R. W. The effects of epinephrine and prostaglandin E-1 on cyclic adenosine 3':5'-monophosphate levels in WI-38 fibroblasts. J Biol Chem. 1974 May 25;249(10):3098–3102. [PubMed] [Google Scholar]
  9. Kram R., Tomkins G. M. Pleiotypic control by cyclic AMP: interaction with cyclic GMP and possible role of microtubules. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1659–1663. doi: 10.1073/pnas.70.6.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kuritz M. J., Polgar P., Taylor L., Rutenburg A. M. The role of adenosine 3':5'-cyclic monophosphate in the division of WI 38 cells. The cellular response to prostaglandin E1 and the effects of an cyclic adenosine 3':5'-cyclic monophosphate analogue and prostaglandin E1 on cell division. Biochem J. 1974 Aug;142(2):339–344. doi: 10.1042/bj1420339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Levine L., Hinkle P. M., Voelkel E. F., Tashjian A. H., Jr Prostaglandin production by mouse fibrosarcoma cells in culture: inhibition by indomethacin and aspirin. Biochem Biophys Res Commun. 1972 May 26;47(4):888–896. doi: 10.1016/0006-291x(72)90576-1. [DOI] [PubMed] [Google Scholar]
  12. Pastan I. H., Johnson G. S., Anderson W. B. Role of cyclic nucleotides in growth control. Annu Rev Biochem. 1975;44:491–522. doi: 10.1146/annurev.bi.44.070175.002423. [DOI] [PubMed] [Google Scholar]
  13. Plagemann P. G., Richey D. P. Transport of nucleosides, nucleic acid bases, choline and glucose by animal cells in culture. Biochim Biophys Acta. 1974 Dec 16;344(3-4):263–305. doi: 10.1016/0304-4157(74)90010-0. [DOI] [PubMed] [Google Scholar]
  14. Plagemann P. G., Sheppard J. R. Competitive inhibition of the transport of nucleosides, hypoxanthine, choline and deoxyglucose by theophylline, papaverine and prostaglandins. Biochem Biophys Res Commun. 1974 Feb 27;56(4):869–875. doi: 10.1016/s0006-291x(74)80269-x. [DOI] [PubMed] [Google Scholar]
  15. Roller B. A., Hirai K., Defendi V. Effect of cAMP on nucleoside metabolism. II. Cell cycle dependence of thymidine transport. J Cell Physiol. 1974 Dec;84(3):333–342. doi: 10.1002/jcp.1040840302. [DOI] [PubMed] [Google Scholar]
  16. Schneider E. L., Stanbridge E. J., Epstein C. J. Incorporation of 3H-uridine and 3H-uracil into RNA: a simple technique for the detection of mycoplasma contamination of cultured cells. Exp Cell Res. 1974 Mar 15;84(1):311–318. doi: 10.1016/0014-4827(74)90411-x. [DOI] [PubMed] [Google Scholar]
  17. Sheppard J. R., Plagemann P. G. Cyclic AMP, membrane transport and cell division. I. Effects of various chemicals on cyclic AMP levels and rate of transport of neucleosides, hypoxanthine and deoxyglucose in several lines of cultured cells. J Cell Physiol. 1975 Apr;85(2 Pt 1):163–172. doi: 10.1002/jcp.1040850202. [DOI] [PubMed] [Google Scholar]
  18. Steiner A. L., Kipnis D. M., Utiger R., Parker C. Radioimmunoassay for the measurement of adenosine 3',5'-cyclic phosphate. Proc Natl Acad Sci U S A. 1969 Sep;64(1):367–373. doi: 10.1073/pnas.64.1.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weber M. J., Rubin H. Uridine transport and RNA synthesis in growing and in density-inhibited animal cells. J Cell Physiol. 1971 Apr;77(2):157–168. doi: 10.1002/jcp.1040770205. [DOI] [PubMed] [Google Scholar]
  20. de Asua L. J., Rozengurt E., Dulbecco R. Kinetics of early changes in phosphate and uridine transport and cyclic AMP levels stimulated by serum in density-inhibited 3T3 cells. Proc Natl Acad Sci U S A. 1974 Jan;71(1):96–98. doi: 10.1073/pnas.71.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES