Summary
The effects of adrenalectomy and cortisone replacement in rats on the activities of adenyl cyclase and phosphodiesterase in homogenates of isolated fat cells and on the accumulation of cyclic 3′,5′-AMP in intact cells were studied.
-
1.
Adrenalectomy caused a decrease in the activity of norepinephrine- and fluoride-stimulated adenyl cyclase in homogenates of isolated fat cells. This decrease was not significantly reversed by pretreatment of the animals with cortisone in vivo.
-
2.
Adrenalectomy caused an increase in the activity of phosphodiesterase. This increase was not reversed by pretreatment of the animals with cortisone for 4 h in vivo but was reversed after 18 h. Incubation of cells from adrenalectomized animals with cortisone in vitro caused no change in phosphodiesterase activity.
-
3.
The incorporation of prelabelled nucleotides into cyclic 3′,5′-AMP was significantly reduced in intact cells from adrenalectomized rats. Pretreatment of the animals with cortisone in vivo for 4 h completely restored the ability of the cells to accumulate radiolabelled cyclic 3′,5′-AMP upon stimulation by norepinephrine.
The experiments underline the difficulties in comparing activation patterns of enzymes under optimal conditions with those occurring in the intact cell. The nature of the lesion in lipolysis caused by adrenalectomy and the reversal of this lesion by cortisone replacement can be demonstrated in the intact cell only.
Similar content being viewed by others
References
Birnbaumer, L., Rodbell, M.: Adenyl cyclase in fat cells. II. Hormone receptors. J. biol. Chem. 244, 3477–3482 (1969).
Blecher, M., Merlino, N. S., Ro'ane, J. T.: Control of the metabolism and lipolytic effect of cyclic 3′,5′-adenosine monophosphate in adipose tissue by insulin, methylxanthines, and nicotinic acid. J. biol. Chem. 243, 3973–3977 (1968).
Brodie, B. B., Krishna, G., Hynie, S.: On the role of adenyl cyclase in the regulation of lipolysis in fasting. Biochem. Pharmacol. 18, 1129–1134 (1969).
—, Maickel, R. P., Stern, D. N.: Autonomic nervous system and adipose tissue. In: Handbook of Physiology, Section 5, Adipose Tissue, pp. 583–600. (Renold, Cahill, Ed.). Baltimore: Williams & Wilkins 1965.
Brooker, G., Thomas, L. J., Appleman, M. M.: The assay of adenosine 3′,5′-cyclic monophosphate and guanosine 3′,5′-cyclic monophosphate in biological materials by enzymatic radioisotope displacement. Biochemistry 7, 4177–4181 (1968).
Butcher, R. W., Ho, R. J., Meng, H. C., Sutherland, E. W.: Adenosine 3′,5′-monophosphate in biological materials. II. The measurement of adenosine 3′,5′-monophosphate in tissues and the role of cyclic nucleotide in the lipolytic response of fat to epinephrine. J. biol. Chem. 240, 4515–4523 (1965).
Butcher, R. W., Baird, C. E.: Effects of prostaglandins on adenosine 3′,5′-monophosphate levels in fat and other tissues. J. biol. Chem. 243, 1713–1717 (1968).
——, 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).
Corbin, J. D., Park, C. R.: Permissive effects of glucocorticoids on lipolysis in adipose tissue. Fed. Proc. 28, 702 (1969).
Ditzion, B. R., Paul, M. I., Pauk, G. L.: Measurement of adenosine 3′,5′-monophosphate (cyclic AMP) in brain. Pharmacology 3, 25–31 (1970).
Garrahan, P. J., Glynn, I. M.: The incorporation of inorganic phosphate into adenosine triphosphate by reversal of the sodium pump. J. Physiol. (Lond.) 192, 237–256 (1967).
Hynie, S., Krishna, G., Brodie, B. B.: Theophylline as a tool in studies of the role of cyclic adenosine 3′,5′-monophosphate in hormone-induced lipolysis. J. Pharmacol. exp. Ther. 153, 90–96 (1966).
Kuo, J. F., DeRenzo, E. C.: A comparison of the effects of lipolytic and antilipolytic agents on adenosine 3′,5′-monophosphate levels in adipose cells as determined by prior labelling with adenine-8-14C. J. biol. Chem. 244, 2252–2260 (1969).
Maickel, R. P., Stern, D. N., Takabatake, E., Brodie, B. B.: The sympathetic nervous system as a hemeostatic mechanism. II. Effect of adrenocortical hormones on body temperature maintenance of cold-exposed adrenalectomized rats. J. Pharmacol. exp. Ther. 157, 111–116 (1967).
Rizack, M. A.: Activation of an epinephrine-sensitive lipolytic activity from adipose tissue by adenosine 3′,5′-phosphate. J. biol. Chem. 239, 392–395 (1964).
Rodbell, M.: Metabolism of isolated fat cells. V. Preparation of “ghosts” and their properties; adenyl cyclase and other enzymes. J. biol. Chem. 242, 5744–5750 (1967).
—: Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J. biol. Chem. 239, 375–381 (1964).
Schönhöfer, P. S., Skidmore, I. F.: Mechanismus der Glucocorticoidwirkung bei der Lipolyse. Hoppe-Seylers Z. physiol. Chem. 351, 1323–1324 (1970).
——: Studies on the conditions of cyclic AMP formation in homogenized and intact fat cells by use of 3H-ATP and 3H-adenine. Pharmacology 6, 109–125 (1971b).
——, Bourne, H. R.: Permissive und nicht-permissive Wirkungen der Glucocorticoide auf das lipolytische System der Fettzelle. Naunyn-Schmiedebergs Arch. Pharmak. 269, 464–465 (1971a).
Schönhöfer, P. S., Skidmore, I. F., Bourne, H. R., Krishna, G.: Cyclic 3′,5′-AMP phosphodiesterase in isolated fat cells. I. Simple and sensitive methods for the assay of phosphodiesterase activity in fat cells and studies on the enzyme inhibition by theophylline. Pharmacology (in press) (1972).
——, Krishna, G., Brodie, B. B.: Lipolysis, adenyl cyclase and cAMP phosphodiesterase in fat cells from adrenalectomized rats. Fed. Proc. 28, 474 (1969).
Senft, G., Schultz, G., Munske, K., Hoffmann, M.: Effects of glucocorticoids and insulin on 3′,5′-AMP phosphodiesterase activity in adrenalectomized rats. Diabetologia 4, 330–335 (1968).
Skidmore, I. F., Schönhöfer, P. S., Bourne, H. R., Krishna, G.: Effect of adrenalectomy and cortisone replacement on the lipolysis in fat tissue and fat cells. (Submitted for publication, 1972.)
Vaughan, M., Murad, F.: Adenyl cyclase activity in particles from fat cells. Biochemistry 8, 3092–3099 (1969).
Weiss, B., Davies, J. I., Brodie, B. B.: Evidence for a role of adenosine 3′,5′-monophosphate in adipose tissue lipolysis. Biochem. Pharmacol. 15, 1553–1561 (1966).
—, Maickel, R. P.: Sympathetic nervous control of adipose tissue lipolysis. Int. J. Neuropharmacol. 7, 393–403 (1965).
Westermann, E.: Die Lipolyse und ihre pharmakologische Beeinflußbarkeit. In: Fette in der Medizin, 7. Folge. S. 8–13. N. Henning and G. Berg, eds. Lochham: Pallas 1965.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schönhöfer, P.S., Skidmore, I.F., Paul, M.I. et al. Effects of glucocorticoids on adenyl cyclase and phosphodiesterase activity in fat cell homogenates and the accumulation of cyclic AMP in intact fat cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 273, 267–282 (1972). https://doi.org/10.1007/BF00501418
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00501418