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Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

Role of {ie195-1} dimersdimers

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Abstract

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.

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References

  • Ammer H. and Christ T. E. (2002) Identify of adenylyl cyclase isoform determines the G protein mediating chronic opioid-induced adenylyl cyclase supersensitivity. J. Neurochem. 83, 818–827.

    Article  PubMed  CAS  Google Scholar 

  • Avidor-Reiss T., Bayewitch M., Levy R., Matus-Leibovitch N., Nevo I., and Vogel Z. (1995) Adenylylcyclase supersensitization in mu-opioid receptor-transfected Chinese hamster ovary cells following chronic opioid treatment. J. Biol. Chem. 270, 29732–29738.

    Article  PubMed  CAS  Google Scholar 

  • Avidor-Reiss T., Nevo I., Levy R., Pfeuffer T., and Vogel Z. (1996) Chronic opioid treatment induces adenylyl cyclase V superactivation. Involvement of Gbetagamma. J. Biol. Chem. 271, 21309–21315.

    Google Scholar 

  • Avidor-Reiss T., Nevo I., Saya D., Bayewitch M., and Vogel Z. (1997) Opiate-induced adenylyl cyclase superactivation is isozyme-specific. J. Biol. Chem. 272, 5040–5047.

    Article  PubMed  CAS  Google Scholar 

  • Bayewitch M. L., Avidor-Reiss T., Levy R., Pfeuffer T., Nevo I., Simonds W. F., and Vogel Z. (1998a) Differential modulation of adenylyl cyclases I and II by various G beta subunits. J. Biol. Chem. 273, 2273–2276.

    Article  PubMed  CAS  Google Scholar 

  • Bayewitch M. L., Avidor-Reiss T., Levy R., Pfeuffer T., Nevo I., Simonds W. F., and Vogel Z. (1998b) Inhibition of adenylyl cyclase isoforms V and VI by various Gbetagamma subunits. FASEB J. 12, 1019–1025.

    PubMed  CAS  Google Scholar 

  • Cali J. J., Zwaagstra J. C., Mons N., Cooper D. M., and Krupinski J. (1994) Type VIII adenylyl cyclase. A Ca2+/calmodulin-stimulated enzyme expressed in discrete regions of rat brain. J. Biol. Chem. 269, 12190–12195.

    PubMed  CAS  Google Scholar 

  • Choi E. J., Xia Z., Villacres E. C., and Storm D. R. (1993) The regulatory diversity of the mammalian adenylyl cyclases. Curr. Opin. Cell Biol. 5, 269–273.

    Article  PubMed  CAS  Google Scholar 

  • Clapham D. E. and Neer E. J. (1997) G protein beta gamma subunits. Annu. Rev. Pharmacol. Toxicol. 37, 167–203.

    Article  PubMed  CAS  Google Scholar 

  • Crespo P., Cachero T. G., Xu N., and Gutkind J. S. (1995) Dual effect of beta-adrenergic receptors on mitogen-activated protein kinase. Evidence for a beta gamma-dependent activation and a G alpha s-cAMP-mediated inhibition. J. Biol. Chem. 270, 25259–25265.

    Article  PubMed  CAS  Google Scholar 

  • Crespo P., Xu N., Simonds W. F., and Gutkind J. S. (1994) Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. Nature 369, 418–420.

    Article  PubMed  CAS  Google Scholar 

  • Federman A. D., Conklin B. R., Schrader K. A., Reed R. R., and Bourne H. R. (1992) Hormonal stimulation of adenylyl cyclase through Gi-protein beta gamma subunits. Nature 356, 159–161.

    Article  PubMed  CAS  Google Scholar 

  • Garritsen A. and Simonds W. F. (1994) Multiple domains of G protein beta confer subunit specificity in beta gamma interaction. J. Biol. Chem. 269, 24418–24423.

    PubMed  CAS  Google Scholar 

  • Garritsen A., van Galen P. J., and Simonds W. F. (1993) The N-terminal coiled-coil domain of beta is essential for gamma association: a model for G-protein beta gamma subunit interaction. Proc. Natl. Acad. Sci. U. S. A. 90, 7706–7710.

    Article  PubMed  CAS  Google Scholar 

  • Hamprecht B. (1977) Structural, electrophysiological, biochemical, and pharmacological properties of neuroblastoma-glioma cell hybrids in cell culture. Int. Rev. Cytol. 49, 99–170.

    Article  PubMed  CAS  Google Scholar 

  • Johnston C. A. and Watts V. J. (2003) Sensitization of adenylate cyclase: a general mechanism of neuroadaptation to persistent activation of Galpha(i/o)-coupled receptors? Life Sci. 73, 2913–2925.

    Article  PubMed  CAS  Google Scholar 

  • Jones S. B. and Bylund D. B. (1988) Characterization and possible mechanisms of alpha 2-adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production in HT29 cells. J. Biol. Chem. 263, 14236–14244.

    PubMed  CAS  Google Scholar 

  • Law S. F., Yasuda K., Bell G. I., and Reisine T. (1993) Gi alpha 3 and G(o) alpha selectively associate with the cloned somatostatin receptor subtype SSTR2. J. Biol. Chem. 268, 10721–10727.

    PubMed  CAS  Google Scholar 

  • Mons N. and Cooper D. M. (1995) Adenylate cyclases: critical foci in neuronal signaling. Trends Neurosci. 18, 536–542.

    Article  PubMed  CAS  Google Scholar 

  • Nestler E. J. (1997) Molecular mechanisms underlying opiate addiction: implication for medications development. Semin. Neurosci. 9, 84–93.

    Article  CAS  Google Scholar 

  • Nevo I., Avidor-Reiss T., Levy R., Bayewitch M., Heldman E., and Vogel Z. (1998) Regulation of adenylyl cyclase isozymes on acute and chronic activation of inhibitory receptors. Mol. Pharmacol. 54, 419–426.

    PubMed  CAS  Google Scholar 

  • Nielsen M. D., Chan G. C., Poser S. W., and Storm D. R. (1996) Differential regulation of type I and type VIII Ca2+-stimulated adenylyl cyclases by Gi-coupled receptors in vivo. J. Biol. Chem. 271, 33308–33316.

    Google Scholar 

  • Patel T. B., Du Z., Pierre S., Cartin L., and Scholich K. (2001) Molecular biological approaches to unravel adenylyl cyclase signaling and function. Gene 269, 13–25.

    Article  PubMed  CAS  Google Scholar 

  • Rhee M. H., Bayewitch M., Avidor-Reiss T., Levy R., and Vogel Z. (1998) Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J. Neurochem. 71, 1525–1534.

    Article  PubMed  CAS  Google Scholar 

  • Rhee M. H., Nevo I., Avidor-Reiss T., Levy R., and Vogel Z. (2000) Differential superactivation of adenylyl cyclase isozymes after chronic activation of the CB(1) cannabinoid receptor. Mol. Pharmacol. 57, 746–752.

    PubMed  CAS  Google Scholar 

  • Salomon Y. (1991) Cellular responsiveness to hormones and neurotransmitters: conversion of [3H]adenine to [3H]cAMP in cell monolayers, cell suspensions, and tissue slices. Methods Enzymol. 195, 22–28.

    Article  PubMed  CAS  Google Scholar 

  • Sharma S. K., Klee W. A., and Nirenberg M. (1975) Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance. Proc. Natl. Acad. Sci. U. S. A. 72, 3092–3096.

    Article  PubMed  CAS  Google Scholar 

  • Simonds W. F. (1999) G protein regulation of adenylate cyclase. Trends Pharmacol. Sci. 20, 66–73.

    Article  PubMed  CAS  Google Scholar 

  • Simonds W. F., Butrynski J. E., Gautam N., Unson C. G., and Spiegel A. M. (1991) G-protein beta gamma dimers. Membrane targeting requires subunit coexpression and intact gamma C-A-A-X domain. J. Biol. Chem. 266, 5363–5366.

    PubMed  CAS  Google Scholar 

  • Sunahara R. K. and Taussig R. (2002) Isoforms of mammalian adenylyl cyclase: multiplicities of signaling. Mol. Intervention 2, 168–184.

    Article  CAS  Google Scholar 

  • Sunahara R. K., Dessauer C. W., and Gilman A. G. (1996) Complexity and diversity of mammalian adenylyl cyclases. Annu. Rev. Pharmacol. Toxicol. 36, 461–480.

    Article  Google Scholar 

  • Tang W. J. and Gilman A. G. (1991) Type-specific regulation of adenylyl cyclase by G protein beta gamma subunits. Science 254, 1500–1503.

    Article  PubMed  CAS  Google Scholar 

  • Tang W. J., Iniguez-Lluhi J. A., Mumby S., and Gilman A. G. (1992) Regulation of mammalian adenylyl cyclases by G-protein alpha and beta gamma subunits. Cold Spring Harb. Symp. Quant. Biol. 57, 135–144.

    PubMed  CAS  Google Scholar 

  • Taussig R., Iniguez-Lluhi J. A., and Gilman A. G. (1993a) Inhibition of adenylyl cyclase by Gi alpha. Science 261, 218–221.

    Article  PubMed  CAS  Google Scholar 

  • Taussig R., Quarmby L. M., and Gilman A. G. (1993b) Regulation of purified type I and type II adenylylcyclases by G protein beta gamma subunits. J. Biol. Chem. 268, 9–12.

    PubMed  CAS  Google Scholar 

  • Taussig R., Tang W. J., Hepler J. R., and Gilman A. G. (1994) Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases. J. Biol. Chem. 269, 6093–6100.

    PubMed  CAS  Google Scholar 

  • Thomas J. M. and Hoffman B. B. (1987) Adenylate cyclase supersensitivity: a general means of cellular adaptation to inhibitory agonists? Trends Pharmacol. Sci. 8, 308–311.

    Article  CAS  Google Scholar 

  • Thomas J. M. and Hoffman B. B. (1996) Isoform-specific sensitization of adenylyl cyclase activity by prior activation of inhibitory receptors: role of beta gamma subunits in transducing enhanced activity of the type VI isoform. Mol. Pharmacol. 49, 907–914.

    Google Scholar 

  • Traber J., Gullis R., and Hamprecht B. (1975) Influence of opiates on the levels of adenosine 3′:5′-cyclic monophosphate in neuroblastoma X glioma hybrid cells. Life Sci. 16, 1863–1868.

    Article  PubMed  CAS  Google Scholar 

  • Vogel Z., Barg J., Levy R., Saya D., Heldman E., and Mechoulam R. (1993) Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. J. Neurochem. 61, 352–355.

    Article  PubMed  CAS  Google Scholar 

  • Watts V. J. and Neve K. A. (1996) Sensitization of endogenous and recombinant adenylate cyclase by activation of D2 dopamine receptors. Mol. Pharmacol. 50, 966–976.

    Google Scholar 

  • Zhang S., Coso O. A., Collins R., Gutkind J. S., and Simonds W. F. (1996) A C-terminal mutant of the G protein beta subunit deficient in the activation of phospholipase C-beta. J. Biol. Chem. 271, 20208–20212.

    Google Scholar 

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Correspondence to Zvi Vogel.

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Steiner, D., Avidor-Reiss, T., Schallmach, E. et al. Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase. J Mol Neurosci 27, 195–203 (2005). https://doi.org/10.1385/JMN:27:2:195

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  • DOI: https://doi.org/10.1385/JMN:27:2:195

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