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. 1973 Nov;52(11):2928–2934. doi: 10.1172/JCI107489

Alkaline Phosphatase. POSSIBLE INDUCTION BY CYCLIC AMP AFTER CHOLERA ENTEROTOXIN ADMINISTRATION

Alfred Baker 1,2, Marshall Kaplan 1,2, Daniel V Kimberg 1,2
PMCID: PMC302561  PMID: 4356003

Abstract

The present studies were undertaken to determine the role, if any, of cyclic 3′,5′-adenosine monophosphate (cyclic AMP) as a chemical inducer of rat liver alkaline phosphatase. Cholera enterotoxin, given intravenously to rats, led to a rapid rise in the activity of hepatic adenyl cyclase that was 7½ times greater than control values in 6 h. Cyclic AMP levels were also significantly increased above control values while the activity of cyclic nucleotide phosphodiesterase was unchanged. Hepatic alkaline phosphatase activity was increased 5½ times above control in 12 h, but its rise followed that of adenyl cyclase and cyclic AMP by several hours. Cycloheximide inhibited the rise of hepatic alkaline phosphatase but not that of adenyl cyclase. The administration of glucagon, a known stimulator of hepatic adenyl cyclase, and of dibutyryl cyclic AMP, led to similar striking increases in hepatic alkaline phosphatase activity. This alkaline phosphatase increase was blocked by the prior administration of cycloheximide. Bile duct ligation, a known stimulator of hepatic alkaline phosphatase activity, failed to produce any significant changes in adenyl cyclase or cyclic AMP. Concomitant treatment of rats with bile duct ligation and cholera enterotoxin or bile duct ligation and glucagon, had no additive effect on the increase in hepatic alkaline phosphatase activity, although the increase occurred earlier. These results suggest that: (a) cyclic AMP may act as an inducer of hepatic alkaline phosphatase: (b) the stimulation of hepatic alkaline phosphatase by cholera enterotoxin is mediated by cyclic AMP; (c) the rise in hepatic alkaline phosphatase following bile duct ligation is not mediated by cyclic AMP; (d) the same alkaline phosphatase in rat liver may be induced by two (or more) mechanisms, only one of which requires cyclic AMP.

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Selected References

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  1. Butcher F. R., Scott D. F., Potter V. R. Effect of glucagon on the level of adenosine 3',5'-monophosphate in rat liver: dependence on the route of administration. Endocrinology. 1971 Jul;89(1):130–134. doi: 10.1210/endo-89-1-130. [DOI] [PubMed] [Google Scholar]
  2. De Crombrugghe B., Chen B., Gottesman M., Pastan I., Varmus H. E., Emmer M., Perlman R. L. Regulation of lac mRNA synthesis in a soluble cell-free system. Nat New Biol. 1971 Mar 10;230(10):37–40. doi: 10.1038/newbio230037a0. [DOI] [PubMed] [Google Scholar]
  3. De Crombrugghe B., Perlman R. L., Varmus H. E., Pastan I. Regulation of inducible enzyme synthesis in Escherichia coli by cyclic adenosine 3', 5'-monophosphate. J Biol Chem. 1969 Nov 10;244(21):5828–5835. [PubMed] [Google Scholar]
  4. Dokas L. A., Kleinsmith L. J. Adenosine 3',5'-monophosphate increases capacity for RNA synthesis in rat liver nuclei. Science. 1971 Jun 18;172(3989):1237–1238. doi: 10.1126/science.172.3989.1237. [DOI] [PubMed] [Google Scholar]
  5. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gorman R. E., Bitensky M. W. Selective effects of cholera toxin on the adrenaline responsive component of hepatic adenyl cyclase. Nature. 1972 Feb 25;235(5339):439–440. doi: 10.1038/235439a0. [DOI] [PubMed] [Google Scholar]
  7. Holten D., Kenney F. T. Regulation of tyrosine alpha-ketoglutarate transaminase in rat liver. VI. Induction by pancreatic hormones. J Biol Chem. 1967 Oct 10;242(19):4372–4377. [PubMed] [Google Scholar]
  8. Jost J. P., Hsie A. W., Rickenberg H. V. Regulation of the synthesis of rat liver serine dehydratase by adenosine 3', 5'- cyclic monophosphate. Biochem Biophys Res Commun. 1969 Mar 31;34(6):748–754. doi: 10.1016/0006-291x(69)90242-3. [DOI] [PubMed] [Google Scholar]
  9. Jost J. P., Hsie A., Hughes S. D., Ryan L. Role of cyclic adenosine 3',5'-monophosphate in the induction of hepatic enzymes. I. Kinetics of the induction of rat liver serine dehydratase by cyclic adenosine 3',5'-monophosphate. J Biol Chem. 1970 Jan 25;245(2):351–357. [PubMed] [Google Scholar]
  10. Jost J. P., Khairallah E. A., Pitot H. C. Studies on the induction and repression of enzymes in rat liver. V. Regulation of the rate of synthesis and degradation of serine dehydratase by dietary amino acids and glucose. J Biol Chem. 1968 Jun 10;243(11):3057–3066. [PubMed] [Google Scholar]
  11. Kaplan M. M., Righetti A. Induction of rat liver alkaline phosphatase: the mechanism of the serum elevation in bile duct obstruction. J Clin Invest. 1970 Mar;49(3):508–516. doi: 10.1172/JCI106260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kimberg D. V., Field M., Gershon E., Schooley R. T., Henderson A. Effects of cycloheximide on the response of intestinal mucosa to cholera enterotoxin. J Clin Invest. 1973 Jun;52(6):1376–1383. doi: 10.1172/JCI107310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimberg D. V., Field M., Johnson J., Henderson A., Gershon E. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J Clin Invest. 1971 Jun;50(6):1218–1230. doi: 10.1172/JCI106599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kimberg D. V., Field M., Johnson J., Henderson A., Gershon E. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J Clin Invest. 1971 Jun;50(6):1218–1230. doi: 10.1172/JCI106599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Pastan I., Perlman R. Cyclic adenosine monophosphate in bacteria. Science. 1970 Jul 24;169(3943):339–344. doi: 10.1126/science.169.3943.339. [DOI] [PubMed] [Google Scholar]
  18. Pekarthy J. M., Short J., Lansing A. I., Lieberman I. Function and control of liver alkaline phosphatase. J Biol Chem. 1972 Mar 25;247(6):1767–1774. [PubMed] [Google Scholar]
  19. Righetti A. B., Kaplan M. M. Effects of actinomycin D on rat liver alkaline phosphatase. Proc Soc Exp Biol Med. 1971 Feb;136(2):491–495. doi: 10.3181/00379727-136-35295. [DOI] [PubMed] [Google Scholar]
  20. Schafer D. E., Lust W. D., Sircar B., Goldberg N. D. Elevated concentration of adenosine 3':5'-cyclic monophosphate in intestinal mucosa after treatment with cholera toxin. Proc Natl Acad Sci U S A. 1970 Oct;67(2):851–856. doi: 10.1073/pnas.67.2.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sharp G. W., Hynie S. Stimulation of intestinal adenyl cyclase by cholera toxin. Nature. 1971 Jan 22;229(5282):266–269. doi: 10.1038/229266a0. [DOI] [PubMed] [Google Scholar]
  22. Tornheim K., O'Dell R. G., Prosky L. Effects of cycloheximide on DNA and protein synthesis in rat liver. Proc Soc Exp Biol Med. 1969 Jun;131(2):601–605. doi: 10.3181/00379727-131-33935. [DOI] [PubMed] [Google Scholar]
  23. Vaughan M., Pierce N. F., Greenough W. B., 3rd Stimulation of glycerol production in fat cells by cholera toxin. Nature. 1970 May 16;226(5246):658–659. doi: 10.1038/226658a0. [DOI] [PubMed] [Google Scholar]
  24. Wicks W. D., Kenney F. T., Lee K. L. Induction of hepatic enzyme synthesis in vivo by adenosine 3', 5'-monophosphate. J Biol Chem. 1969 Nov 10;244(21):6008–6013. [PubMed] [Google Scholar]
  25. Wicks W. D. Tyrosine-alpha-ketoglutarate transaminase: induction by epinephrine and adenosine-3',5'-cyclic phosphate. Science. 1968 May 31;160(3831):997–998. doi: 10.1126/science.160.3831.997. [DOI] [PubMed] [Google Scholar]
  26. Yeung D., Oliver I. T. Induction of phosphopyruvate carboxylase in neonatal rat liver by adenosine 3',5'-cyclic monophosphate. Biochemistry. 1968 Sep;7(9):3231–3239. doi: 10.1021/bi00849a028. [DOI] [PubMed] [Google Scholar]

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