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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1977 Jan;74(1):92–95. doi: 10.1073/pnas.74.1.92

Activation of cardiac adenylate cyclase: horminal modification of the magnesium ion requirement.

R Alvarez, J J Bruno
PMCID: PMC393203  PMID: 264697

Abstract

Histamine and epinephrine stimulate the activity of guinea pig heart adenylate cyclase [ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1], in part, by decreasing the requirement for Mg2+ as an activator. This effect may represent an increase in affinity for Mg2+ and/or a decrease in sensitivity of the enzyme towards inhibition by free ATP. Both of these inotropic hormones also increase maximum velocity. Pretreatment of the membrane-bound enzyme with EDTA, to remove available divalent cations, almost eliminates persistent stimulation by guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Addition of Mg2+ to the preincubation medium restores the capacity of Gpp(NH)p to acutely activate the enzyme. These results indicate that Mg2+ interacts with the nucleotide (GTP) regulatory site. Persistent stimulation of the enzyme by either Gpp(NH)p or fluoride ion also involves a decrease in the requirement for Mg2+ and an increase in maximum velocity.

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Selected References

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

  1. Birnbaumer L., Pohl S. L., Rodbell M. Adenyl cyclase in fat cells. 1. Properties and the effects of adrenocorticotropin and fluoride. J Biol Chem. 1969 Jul 10;244(13):3468–3476. [PubMed] [Google Scholar]
  2. Drummond G. I., Duncan L. Adenyl cyclase in cardiac tissue. J Biol Chem. 1970 Mar 10;245(5):976–983. [PubMed] [Google Scholar]
  3. Drummond G. I., Severson D. L., Duncan L. Adenyl cyclase. Kinetic properties and nature of fluoride and hormone stimulation. J Biol Chem. 1971 Jul 10;246(13):4166–4173. [PubMed] [Google Scholar]
  4. Garbers D. L., Johnson R. A. Metal and metal-ATP interactions with brain and cardiac adenylate cyclases. J Biol Chem. 1975 Nov 10;250(21):8449–8456. [PubMed] [Google Scholar]
  5. Hammes G. G., Rodbell M. Simple model for hormone-activated adenylate cyclase systems. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1189–1192. doi: 10.1073/pnas.73.4.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Lin M. C., Salomon Y., Rendell M., Rodbell M. The hepatic adenylate cyclase system. II. Substrate binding and utilization and the effects of magnesium ion and pH. J Biol Chem. 1975 Jun 10;250(11):4246–4252. [PubMed] [Google Scholar]
  8. Londos C., Rodbell M. Multiple inhibitory and activating effects of nucleotides and magnesium on adrenal adenylate cyclase. J Biol Chem. 1975 May 10;250(9):3459–3465. [PubMed] [Google Scholar]
  9. Londos C., Salomon Y., Lin M. C., Harwood J. P., Schramm M., Wolff J., Rodbell M. 5'-Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3087–3090. doi: 10.1073/pnas.71.8.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. O'SULLIVAN W. J., PERRIN D. D. THE STABILITY CONSTANTS OF METAL-ADENINE NUCLEOTIDE COMPLEXES. Biochemistry. 1964 Jan;3:18–26. doi: 10.1021/bi00889a005. [DOI] [PubMed] [Google Scholar]
  11. 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. 1971 Sep;43(1):227–239. doi: 10.1016/0003-2697(71)90128-x. [DOI] [PubMed] [Google Scholar]
  12. Rendell M., Salomon Y., Lin M. C., Rodbell M., Berman M. The hepatic adenylate cyclase system. III. A mathematical model for the steady state kinetics of catalysis and nucleotide regulation. J Biol Chem. 1975 Jun 10;250(11):4253–4260. [PubMed] [Google Scholar]
  13. Rodbell M., Lin M. C., Salomon Y., Londos C., Harwood J. P., Martin B. R., Rendell M., Berman M. Role of adenine and guanine nucleotides in the activity and response of adenylate cyclase systems to hormones: evidence for multisite transition states. Adv Cyclic Nucleotide Res. 1975;5:3–29. [PubMed] [Google Scholar]
  14. Salomon Y., Lin M. C., Londos C., Rendell M., Rodbell M. The hepatic adenylate cyclase system. I. Evidence for transition states and structural requirements for guanine nucloetide activiation. J Biol Chem. 1975 Jun 10;250(11):4239–4245. [PubMed] [Google Scholar]
  15. Severson D. L., Drummond G. I., Sulakhe P. V. Adenylate cyclase in skeletal muscle. Kinetic properties and hormonal stimulation. J Biol Chem. 1972 May 10;247(9):2949–2958. [PubMed] [Google Scholar]
  16. de Haën C. Adenylate cyclase. A new kinetic analysis of the effects of hormones and fluoride ion. J Biol Chem. 1974 May 10;249(9):2756–2762. [PubMed] [Google Scholar]

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