Skip to main content
Log in

Ca2+/CaM-sensitive adenylyl cyclase activity is decreased in the Alzheimer's brain: Possible relation to type I adenylyl cyclase

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Immunoreactivities of four subtypes of adenylyl cyclase (AC) (types I, II, IV and V/VI), and basal, forskolin- and Mn2+-stimulated AC activities with or without calcium and calmodulin (Ca2+/CaM) were estimated in parietal cortex membranes from cases with dementia of the Alzheimer type (DAT) and age-matched controls. Immunoreactivities of AC-I and AC-II were significantly decreased, but those of AC-IV and AC-V/VI did not change in DAT brains. There was a significant correlation of AC-I immunoreactivity with Ca2+/CaM-sensitive AC activity, but not with the Ca2+/CaM-insensitive activity. Ca2+/CaM-sensitive AC activity was significantly lower in DAT than in the control, indicating that impairment of Ca2+/CaM-sensitive AC-I is clearly involved in the pathophysiology of DAT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79: 59–68

    Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254

    Google Scholar 

  • Chetkovich DM, Sweatt JD (1993) NMDA receptor activation increases cyclic AMP in area CA1 of the hippocampus via calcium/calmodulin stimulation of adenylyl cyclase. J Neurochem 61: 1933–1942

    Google Scholar 

  • Cowburn RF, O'Neil C, Ravid R, Alafuzoff I, Winblad B, Flowler CJ (1992a) Adenylyl cyclase activity in postmortem human brain: evidence of altered G protein mediation in Alzheimer's disease. J Neurochem 58: 1409–1419

    Google Scholar 

  • Cowburn RF, O'Neill C, Ravid R, Winblad B, Fowler J (1992b) Preservation of Gi-protein inhibited adenylyl cyclase activity in the brains of patients with Alzheimer's disease. Neurosci Lett 141: 16–20

    Google Scholar 

  • Feinstem PG, Schrader KA, Bakalyar HA, Tang W-J, Krupinski J, Gilman AG, Reed RR (1991) Molecular cloning and characterization of Ca2+/Calmodulin-insensitive adenylyl cyclase from rat brain. Proc Natl Acad Sci USA 88: 10173–10177

    Google Scholar 

  • Gsell W, Lange KW, Pfeuffer R, Heckers S, Heinsen H, Senitz D, Jellinger K, Ransmayr G, Wichart I, Vock R, Beckmann H, Riederer P (1993) How to run a brain bank: a report from the Austro-German brain bank. J Neural Transm [Suppl] 39: 31–70

    Google Scholar 

  • Hummler E, Cole TJ, Blendy JA, Ganss R, Aguzzi A, Schmid W, Beermann F, Schütz G (1994) Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Proc Natl Acad Sci USA 91: 5647–5651

    Google Scholar 

  • Ikezu T, Okamoto T, Komatsuzaki K (1996) Negative transduction of cAMP response element by familial Alzheimer's mutants of APP. EMBO J 15: 2468–2475

    Google Scholar 

  • Iyengar R (1993) Molecular and functional diversity of mammalian Gs-stimulated adenylyl cyclase. FASEB J 7: 768–775

    Google Scholar 

  • Katsushika S, Chen L, Kawabe J, Nilakantan R, Halnon NJ, Homey CJ, Ishikawa Y (1992) Cloning and characterization of a sixth adenylyl isoform: types V and VI constitute a subgroup within the mammalian adenylyl cyclase family. Proc Natl Acad Sci USA 89: 8774–8778

    Google Scholar 

  • Krupinski J, Coussen F, Bakalyar HA, Tang W-J, Feinstein PG, Orth K, Slaughter C, Reed RR, Gilman AG (1989) Adenylyl cyclase amino acid sequence: possible channel-or transporter-like structure. Science 244: 1558–1564

    Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: a report of the NINCDS-ADRDA work group under the auspices of the department of health and human services task force on Alzheimer's disease. Neurology 34: 939–944

    Google Scholar 

  • NcLaughlin M, Ross BM, Milligan G, McCulloch J, Knowler JT (1991) Robustness of G proteins in Alzheimer's disease: an immunoblot study. J Neurochem 57: 9–14

    Google Scholar 

  • Ohm TG, Bohl J, Lemmer B (1991) Reduced basal and stimulated (isoprenaline, Gpp(NH)p, forskolin) adenylate cyclase activity in Alzheimer's disease correlated with histopathological changes. Brain Res 540: 229–236

    Google Scholar 

  • Salomon Y (1979) Adenylate cyclase assay. Adv Cycl Nucl Res 10: 35–55

    Google Scholar 

  • Schnecko A, Witte K, Bohl J, Ohm TG, Lemmer B (1994) Adenylyl cyclase activity in Alzheimer's disease brain: stimulatory and inhibitory signal transduction pathways are differently affected. Brain Res 644: 291–296

    Google Scholar 

  • Seamon KB, Daly JW (1986) Forskolin: its biological and chemical properties. Adv Cycl Nucl Res 20: 1

    Google Scholar 

  • Villacres EC, Wu Z, Hua W, Nielsen MD, Watters JJ, Yan C, Beavo J, Storm DR (1995) Developmentally expressed Ca2+-sensitive adenylyl cyclase activity is disrupted in the brains of type I adenylyl cyclase mutant mice. J Biol Chem 270: 14352–14357

    Google Scholar 

  • Wayman GA, Impey S, Wu Z, Kindsvogel W, Prichard L, Storm DR (1994) Synergisitic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo. J Biol Chem 269: 25400–25405

    Google Scholar 

  • Wu Z, Wong ST, Storm DR (1993) Modification of the calcium and calmodulin sensitivity of the type I adenylyl cyclase by mutagenesis of its calmodulin binding domain. J Biol Chem 268: 23766–23768

    Google Scholar 

  • Wu Z-L, Thomas SA, Villacres EC, Xia Z, Simmons ML, Chavkin C, Palmiter RD, Storm DR (1995) Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice. Proc Natl Acad Sci USA 92: 220–224

    Google Scholar 

  • Xia Z, Choi E-J, Storm DR (1995) Do the calmodulin-stimulated adenylyl cyclases play a role in neuroplasticity? Behav Brain Sci 18: 429–440

    Google Scholar 

  • Yamamoto M, Ozawa H, Saito T, Frölich L, Riederer P, Takahata N (1996) Reduced immunoreactivity of adenylyl cyclases in dementia of the Alzheimer type. Neuroreport 7: 2965–2970

    Google Scholar 

  • Yin JCP, Wallach JS, Del Vecchio M, Wilder EL, Zhou H, Quinn WG, Tully T (1994) Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79: 49–58

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamamoto, M., Ozawa, H., Saito, T. et al. Ca2+/CaM-sensitive adenylyl cyclase activity is decreased in the Alzheimer's brain: Possible relation to type I adenylyl cyclase. J. Neural Transmission 104, 721–732 (1997). https://doi.org/10.1007/BF01291889

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01291889

Keywords

Navigation