Advertisement

Stimulation of cyclic adenosine 3′,5′-monophosphate accumulation and lipolysis in fat cells by adenosine deaminase

  • U. Schwabe
  • R. Ebert
Article

Summary

The basal lipolytic activity of isolated fat cells of the rat was greatly enhanced in the presence of 0.01 to 30 μg adenosine deaminase (ADA) per ml. This effect was more pronounced in dilute (20000 cells/ml) than in concentrated cell suspensions (100000 cells/ml); this is possibly due to the presence, in the incubation medium, of a high concentration of inosine which is formed by the deamination of the large amounts of adenosine released from high concentrations of fat cells. Inosine, although less potent than adenosine as an antilipolytic agent, markedly inhibited ADA-induced lipolysis at concentrations between 10 to 100 μM. The lipolytic effect of ADA was identical with the stimulation of lipolysis by 1 μM noradrenaline or 1 mM theophylline, while 1 mM dibutyryl cyclic AMP yielded two-fold higher values. The effects of ADA and lipolytic agents at maximally stimulating concentrations were not additive.

After 5 min of incubation maximally effective concentrations of ADA which were also maximal with respect to lipolysis caused a 3- to 6-fold elevation of cyclic AMP levels in fat cells. A similar increase was observed with maximally effective concentrations of theophylline, whereas noradrenaline produced a 100- to 200-fold elevation. This indicates that a small accumulation of cyclic AMP may be sufficient to trigger the full lipolytic response. Furthermore, ADA, like theophylline, acted synergistically with noradrenaline and prevented the fall of cyclic AMP levels during 30 min of incubation.

Insulin (100 μU/ml) and nicotinic acid (0.1 μM) decreased cyclic AMP accumulation and glycerol production induced by ADA.

The results support the hypothesis that adenosine is released from isolated fat cells and that this nucleoside may serve as an inhibitor of adenyl cyclase activity, thus regulating cyclic AMP-dependent processes in adipose tissue.

Key words

Cyclic AMP Adenosine Lipolysis Fat Cell Adenosine Deaminase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Butcher, R. W., Baird, C. E., Sutherland, E. W.: Effects of lipolytic and antilipolytic substances on adenosine 3′,5′-monophosphate levels in isolated fat cells. J. biol. Chem.243, 1705–1712 (1968)Google Scholar
  2. Chen, R. F.: Removal of fatty acids from serum albumin by charcoal treatment. J. biol. Chem.242, 173–181 (1967)Google Scholar
  3. Ebert, R., Schwabe, U.: Studies on the antilipolytic effect of adenosine and related compounds in isolated fat cells. Naunyn-Schmiedeberg's Arch. Pharmacol.278, 247–259 (1973)Google Scholar
  4. Fain, J. N.: Biochemical aspects of drug and hormone action on adipose tissue. Pharmacol. Rev.25, 67–118 (1973a)Google Scholar
  5. Fain, J. N.: Inhibition of adenosine cyclic 3′,5′-monophosphate accumulation in fat cells by adenosine, N6-(phenylisopropyl) adenosine and related compounds. Molec. Pharmacol.9, 595–604 (1973b)Google Scholar
  6. Fain, J. N., Pointer, R. H., Ward, W. F.: Effects of adenosine nucleosides on adenylate cyclase, phosphodiesterase, cyclic adenosine monophosphate accumulation and lipolysis in fat cells. J. biol. Chem.247, 6866–6872 (1972)Google Scholar
  7. Friedkin, M., Kalckar, H.: Nucleoside phosphorylases. In: P. D. Boyer, H. A. Lardy and K. Myrbäck (eds.) The enzymes, vol. 5, pp. 237–255. New York: Academic Press 1961Google Scholar
  8. Gilman, A. G.: A protein binding assay for adenosine 3′,5′-cyclic monophosphate. Proc. nat. Acad. Sci. (Wash.)67, 305–312 (1970)Google Scholar
  9. Hittelman, K. J., Wu, C. F., Butcher, R. W.: Control of cyclic AMP levels in isolated fat cells from hamsters. Biochim. biophy. Acta (Amst.)304, 188–196 (1973)Google Scholar
  10. Ho, R. J., Sutherland, E. W.: Formation and release of a hormone antagonist by rat adipocytes. J. biol. Chem.246, 6822–6827 (1971)Google Scholar
  11. Katocs, A. S., Largis, E. E., Allen, D. O., Ashmore, J.: Perifused fat cells. Effect of lipolytic agents. J. biol. Chem.248, 5089–5094 (1973)Google Scholar
  12. Lambert M., Neish, A. C.: Rapid method for estimation of glycerol in fermentation solutions. Canad. J. Res., Sect. B28, 83–89 (1950)Google Scholar
  13. McKenzie, S. G., Bär, H. P.: On the mechanism of adenyl cyclase inhibition by adenosine. Canad. J. Physiol. Pharmacol.51, 190–196 (1973)Google Scholar
  14. Mosinger, B., Vaughan, M.: Effects of electrolytes on epinephrine stimulated lipolysis in adipose tissue in vitro. Biochim. biophys. Acta (Amst.)144, 556–568 (1967)Google Scholar
  15. Nash, T.: The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem. J.55, 416–421 (1953)Google Scholar
  16. Rodbell, M.: Metabolism of isolated fat cells. I. Effect of hormones on glucose metabolism and lipolysis. J. biol. Chem.239, 375–380 (1964)Google Scholar
  17. Schwabe, U., Ebert, R.: Different effects of lipolytic hormones and phosphodiesterase inhibitors on cyclic 3′,5′-AMP levels in isolated fat cells. Naunyn-Schmiedeberg's Arcy. Pharmacol.274, 287–298 (1972)Google Scholar
  18. Schwabe, U., Ebert, R., Erbler, H. C.: Adenosine release from isolated fat cells and its significance for the effects of hormones on cyclic 3′,5′-AMP levels and lipolysis. Naunyn-Schmiedeberg's Arch. Pharmacol.276, 133–148 (1973)Google Scholar
  19. Stock, K., Prilop, M.: Dissociation of catecholamine-induced formation of adenosine 3′,5′-monophosphate and release of glycerol in fat cells by prostaglandinE 1,E 2 andN 6-phenylisopropyladenosine. Naunyn-Schmiedeberg's Arch. Pharmacol.282, 15–31 (1974)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • U. Schwabe
    • 1
  • R. Ebert
    • 1
  1. 1.Institut für PharmakologieMedizinische Hochschule HannoverHannover-KleefeldGermany

Personalised recommendations