Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 310, Issue 3, pp 231–236 | Cite as

Effects of dimethyl sulfoxide and other dipolar aprotic solvents on rat hepatic adenylate cyclase. Potentiating effects on glucagon and guanylylimidodiphosphate stimulation

  • S. Hynie
  • V. Klenerová


The actions of dimethyl sulfoxide (DMSO), acetone and two other aprotic solvents on the activity of rat hepatic adenylate cyclase were studied in order to detect their possible effects on both hormonal and nonhormonal enzyme stimulation. The glucagonor guanylylimidodiphosphate [Gpp(NH)p]-stimulated activity was significantly increased by all DMSO concentrations (0.08–2.57 M) while the highest concentrations of this solvent decreased the enzyme activity stimulated by sodium fluoride. The effect of DMSO on adneylate cyclase activity is reversible and the stimulatory effect of this drug can be seen even on adenylate cyclase activity in the persistent active state induced by preincubation of the enzyme with Gpp(NH)p. An increase in adenylate cyclase activity stimulated by glucagon or Gpp(NH)p was also seen after the addition of other aprotic solvents (acetone, acetonitrile and dimethylformamide) to the assay system. These effects of aprotic solvents on the rat hepatic adenylate cyclase activity may be caused by an increase of membrane fluidity and facilitated movement of the adenylate cyclase subunits in the plane of the cell membrane.

Key words

Rat liver Adenylate cyclase Glucagon Guanylylimidodiphosphate Dimethyl sulfoxide Aprotic solvents 


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  1. Cuatreasas, P.: Hormone receptors — their function in cell membranes and some problems related to methodology. In: Advances in cyclic nucleotide research, Vol. 5 (G. I. Drummond, P. Greengard, G. A. Robison, eds.), pp. 79–104. New York: Raven Press 1975Google Scholar
  2. David, N. A.: The pharmacology of dimethyl sulfoxide. Ann. Rev. Pharmacol. 12, 353–374 (1972)Google Scholar
  3. Gorman, R. E., Bitensky, M. W.: Selective activation by short chain alcohols of glucagon responsive adenyl cyclase in liver. Endocrinology 87, 1075–1081 (1970)Google Scholar
  4. Greene, H. L., Herman, R. H., Kraemer, S.: Stimulation of jejunal adenyl cyclase by ethanol. J. Lab. Clin. Med. 78, 336–342 (1971)Google Scholar
  5. Helmreich, E. J. M.: Hormone-receptor interactions. FEBS Lett. 61, 1–5 (1976)Google Scholar
  6. Helmreich, E. J. M., Pfeuffer, T.: Signal transmission from hormone receptors to adenylate cyclase: Synopsis and hypothesis. In: Cell membrane receptors for drugs and hormones: A multidisciplinary approach (R. W. Straub, L. Bolis, eds.), pp. 119–127 New York: Raven Press 1978Google Scholar
  7. Hynie, S.: Simple and quick assay of guanylate cyclase. Collections Czechoslov. Chem. Commun. 39, 2325–2332 (1974)Google Scholar
  8. Hynie, S., Elisová, K., Lincová, D., Ĉepelík J.: Solubilisace adenyl cyklasy Lubrolem PX a Tritonem X 100; detekce stupnê solubilisace sorbitolem. Ĉs. Fysiol. 21, 276–277 (1972)Google Scholar
  9. Hynie, S., Lanefelt, F., Fredholm, B. B.: Effects of ethanol on human lymphocyte levels of cyclic AMP in vitro; the potentiating effect on isoproterenol, prostaglandin E2 or adenosine stimulation. Acta Pharmacol. Toxicol. (in press, 1979)Google Scholar
  10. Hynie, S., Ledvina, M., Smrt J.: Esters of adenosine 5′-phosphate as coproducts of adenosine 3′,5′-cyclic phosphate in reactions of ATP with adenylate cyclase in the presence of hydroxy derivatives. Collections Czechoslov. Chem. Commun. 41, 1448–1458 (1976)Google Scholar
  11. Hynie, S., Sharp, G. W. G.: Adenyl cyclase in the toad bladder. Biochim. Biophys. Acta 230, 231–235 (1971)Google Scholar
  12. Hynie, S., Wenke, M.: The absence of stimulation of lipolysis by papaverine, a strong inhibitor of phosphodiesterase. Eur. J. Pharmacol. 30, 230–237 (1975)Google Scholar
  13. Kiss, Z., Hanoune, J.: Synthesis and decomposition of alcohol esters of 5′-AMP by rat liver plasma membrane. Biochim. Biophys. Acta 538, 458–472 (1978)Google Scholar
  14. Lowry, O. H., Rosenbrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin-phenol reagent. J. Biol. Chem. 193, 265–275 (1951)Google Scholar
  15. Orly, J., Schramm, M.: Fatty acids as modulators of membrane functions: catecholamine-activated adenylate cyclase of the turkey erythrocyte. Proc. Natl. Acad. Sci. USA 72, 3433–3437 (1975)Google Scholar
  16. Perkins, J. P.: Adenyl cyclase. In: Advances in cyclic nucleotide research, Vol. 3 (P. Greengard, G. A. Robison, eds.), pp. 1–64. New York: Raven Press 1973Google Scholar
  17. Petrack, B., Ma, D., Sheppy, F.: Formation of a novel nucleotide by fat cell preparations containing adenylate cyclase. J. Biol. Chem. 249, 3661–3663 (1974)Google Scholar
  18. Ramachandran, J.: A new simple method for separation of adenosine 3′,5′-cyclic monophosphate from other nucleotides and its use in the assay of adenyl cyclase. Anal. Biochem. 43, 227–239 (1971)Google Scholar
  19. Rimon, G., Hanski, E., Braun, S., Levitzki, A.: Mode of coupling between hormone receptors and adenylate cyclase elucidated by modulation of membrane fluidity. Nature 276, 394–396 (1978)Google Scholar
  20. Ryan, J., Rogers, G. N., Toscano, D. G., Storm, D. R.: Formation of adenosine 5′-phosphoroglycerol from ATP and glycerol by rat liver plasma membranes. J. Biol. Chem. 252, 1719–1722 (1977)Google Scholar
  21. Shinitzky, M., Inbar, M.: Microviscosity parameters and protein mobility in biological membranes. Biochim. Biophys. Acta 433, 133–149 (1976)Google Scholar
  22. Stock, K., Schmidt, M.: Effects of short-chain alcohols on adenylate cyclase in plasma membranes of rat adipocytes. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 37–43 (1978)Google Scholar
  23. Van Obberghen, E., De Meyts, P., Roth, J.: Inhibition of insulin receptor binding by dimethyl sulfoxide. Biochim. Biophys. Acta 582, 486–495 (1979)Google Scholar
  24. Volicer, L., Gold, B. I.: Interactions of ethanol with cyclic AMP. Adv. Exp. Med. Biol. 56, 211–237 (1975)Google Scholar
  25. Volicer, L., Hynie, S.: Effect of catecholamines and angiotensin on cyclic AMP in rat aorta and tail artery. Eur. J. Pharmacol. 15, 214–220 (1971)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • S. Hynie
    • 1
  • V. Klenerová
    • 1
  1. 1.Institutes of Pharmacology and Pathological Physiology, Faculty of General MedicineCharles UniversityPrague 2Czechoslovakia

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