Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1982 Apr 15;204(1):25–30. doi: 10.1042/bj2040025

Modulation of collagen production by fibroblasts. Effects of chronic exposure to agonists that increase intracellular cyclic AMP.

L E Saltzman, J Moss, R A Berg, B Hom, R G Crystal
PMCID: PMC1158311  PMID: 6288014

Abstract

Cultured human lung fibroblasts were evaluated for their responsiveness to isoprenaline (isoproterenol) or prostaglandin E2 before and after chronic incubation with the agonist. Cells incubated for 6 h with either agonist were suppressed in terms of collagen production and exhibited increased intracellular cyclic AMP. Cells incubated for 72 h with the agonist and then re-challenged for 6 h with the same agonist did not demonstrate suppressed collagen production or increased cyclic AMP. Cells incubated for 72 h with isoprenaline still responded to prostaglandin E2 when challenged for 6 h; however, when the order of agonist exposure was reversed, cells incubated with prostaglandin E2 did not respond to a challenge by isoprenaline. If cells were allowed to recover for 48 h without the agonist after a 72 h chronic incubation, they recovered their responsiveness to the agonist. The results indicate that, although cultured fibroblasts may become desensitized to one agonist, they may retain their sensitivity to a second agonist and chronic suppression of collagen production may be achieved by alternate exposure to isoprenaline and prostaglandin E2.

Full text

PDF
28

Selected References

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

  1. Baum B. J., Moss J., Breul S. D., Berg R. A., Crystal R. G. Effect of cyclic AMP on the intracellular degradation of newly synthesized collagen. J Biol Chem. 1980 Apr 10;255(7):2843–2847. [PubMed] [Google Scholar]
  2. Baum B. J., Moss J., Breul S. D., Crystal R. G. Association in normal human fibroblasts of elevated levels of adenosine 3':5'-monophosphate with a selective decrease in collagen production. J Biol Chem. 1978 May 25;253(10):3391–3394. [PubMed] [Google Scholar]
  3. Breul S. D., Bradley K. H., Hance A. J., Schafer M. P., Berg R. A., Crystal R. G. Control of collagen production by human diploid lung fibroblasts. J Biol Chem. 1980 Jun 10;255(11):5250–5260. [PubMed] [Google Scholar]
  4. Chlapowski F. J., Kelly L. A., Butcher R. W. Cyclic nucleotides in cultured cells. Adv Cyclic Nucleotide Res. 1975;6:245–338. [PubMed] [Google Scholar]
  5. Hance A. J., Crystal R. G. Rigid control of synthesis of collagen types I and III by cells in culture. Nature. 1977 Jul 14;268(5616):152–154. doi: 10.1038/268152a0. [DOI] [PubMed] [Google Scholar]
  6. Hassell T. M., Page R. C., Narayanan A. S., Cooper C. G. Diphenylhydantoin (dilantin) gingival hyperplasia: drug-induced abnormality of connective tissue. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2909–2912. doi: 10.1073/pnas.73.8.2909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hsie A. W., Jones C., Puck T. T. Further changes in differentiation state accompanying the conversion of Chinese hamster cells of fibroblastic form by dibutyryl adenosine cyclic 3':5'-monophosphate and hormones. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1648–1652. doi: 10.1073/pnas.68.7.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Johnson G. L., Wolfe B. B., Harden T. K., Molinoff P. B., Perkins J. P. Role of beta-adrenergic receptors in catecholamine-induced desensitization of adenylate cyclase in human astrocytoma cells. J Biol Chem. 1978 Mar 10;253(5):1472–1480. [PubMed] [Google Scholar]
  9. Levitzki A., Helmreich E. J. Hormone-receptor--adenylate cyclase interactions. FEBS Lett. 1979 May 15;101(2):213–219. doi: 10.1016/0014-5793(79)81011-x. [DOI] [PubMed] [Google Scholar]
  10. Levitzki A. The mode of coupling of adenylate cyclase to hormone receptors and its modulation by GTP. Biochem Pharmacol. 1978;27(17):2083–2088. doi: 10.1016/0006-2952(78)90276-9. [DOI] [PubMed] [Google Scholar]
  11. Manner G., Goldring I. P., Kuleba M. Effect of proteolytic enzymes on collagen and non-collagen protein synthesis in human lung fibroblasts. Connect Tissue Res. 1974;2(4):283–290. doi: 10.3109/03008207409152257. [DOI] [PubMed] [Google Scholar]
  12. Mickey J., Tate R., Lefkowitz R. J. Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro. J Biol Chem. 1975 Jul 25;250(14):5727–5729. [PubMed] [Google Scholar]
  13. Narayanan A. S., Page R. C. Serum modulates collagen types in human gingiva fibroblasts. FEBS Lett. 1977 Aug 1;80(1):221–224. doi: 10.1016/0014-5793(77)80444-4. [DOI] [PubMed] [Google Scholar]
  14. Newcombe D. S., Ciosek C. P., Jr, Ishikawa Y., Fahey J. V. Human synoviocytes: activation and desensitization by prostaglandins and 1-epinephrine. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3124–3128. doi: 10.1073/pnas.72.8.3124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Peterkofsky B., Prather W. B. Increased collagen synthesis in Kirsten sarcoma virus-transformed BALB 3T3 cells grown in the presence of dibutyryl cyclic AMP. Cell. 1974 Nov;3(3):291–299. doi: 10.1016/0092-8674(74)90144-5. [DOI] [PubMed] [Google Scholar]
  16. Peterkofsky B., Prather W. Increased proline transport resulting from growth of normal and Kirsten sarcoma virus-transformed BALB 3T3 cells in the presence of N(6), O(2')-dibutyryl cyclic adenosine 3',5'-monophosphate. Arch Biochem Biophys. 1979 Feb;192(2):500–511. doi: 10.1016/0003-9861(79)90120-6. [DOI] [PubMed] [Google Scholar]
  17. Shear M., Insel P. A., Melmon K. L., Coffino P. Agonist-specific refractoriness induced by isoproterenol. Studies with mutant cells. J Biol Chem. 1976 Dec 10;251(23):7572–7576. [PubMed] [Google Scholar]
  18. Su Y. F., Cubeddu L., Perkins J. P. Regulation of adenosine 3':5'-monophosphate content of human astrocytoma cells: desensitization to catecholamines and prostaglandins. J Cyclic Nucleotide Res. 1976 Jul-Aug;2(4):257–270. [PubMed] [Google Scholar]
  19. Tuck M. L., Fittingoff D., Connelly M., Krall J. F. beta-adrenergic catecholamine regulation of lymphocyte sensitivity: heterologous desensitization to prostaglandin E2 by isoproterenol. J Clin Endocrinol Metab. 1980 Jul;51(1):1–6. doi: 10.1210/jcem-51-1-1. [DOI] [PubMed] [Google Scholar]
  20. Uitto J., Lichtenstein J. R. Defects in the biochemistry of collagen in diseases of connective tissue. J Invest Dermatol. 1976 Feb;66(02):59–79. doi: 10.1111/1523-1747.ep12481404. [DOI] [PubMed] [Google Scholar]

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

RESOURCES