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Gene Review

Adcy1  -  adenylate cyclase 1

Mus musculus

Synonyms: AC1, ATP pyrophosphate-lyase 1, Adenylate cyclase type 1, Adenylate cyclase type I, Adenylyl cyclase 1, ...
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Disease relevance of Adcy1

  • Thus, AC1 and AC8 are critical modulators of neurodegeneration induced by activity blockade in the neonatal brain and represent genetic loci that may potentially modify the severity of fetal alcohol syndrome [1].
  • Our findings provide direct evidence that AC1 plays an important role in neuronal excitotoxicity and may serve as a therapeutic target for preventing excitotoxicity in stroke and neurodegenerative diseases [2].
  • The ganglion cell layer and the inner nuclear layer (INL) were immunoreactive for both Ca(2+)-sensitive (AC1, AC3) and Ca(2+)-insensitive (AC2, AC4) isoforms of adenylyl cyclase [3].
  • A nucleotide regulatory site for somatostatin inhibition of adenylate cyclase in S49 lymphoma cells [4].
  • In the course of examining stimulation of the B16 murine melanoma adenylate cyclase by melanocyte-stimulating hormone (MSH) and by the diterpene forskolin, we noted that tumour cell clones isolated from common parent cell populations differed widely in their responses to these agonists [5].

Psychiatry related information on Adcy1


High impact information on Adcy1

  • We identified adenylyl cyclase type I (Adcy1) as the gene disrupted in brl mutant mice by fine mapping of proximal chromosome 11, enzyme assay, mutation analysis and examination of mice homozygous for a targeted disruption of Adcy1 [10].
  • Crhr1 is highly expressed in the anterior pituitary, neocortex, hippocampus, amygdala and cerebellum, and activation of this receptor stimulates adenylate cyclase [11].
  • Increased expression of the c-fos proto-oncogene, presumably a consequence of increased adenylate cyclase activity, may be important in the pathogenesis of the bone lesions in patients with fibrous dysplasia [12].
  • Development of activatable adenylate cyclase in the preimplantation mouse embryo and a role for cyclic AMP in blastocoel formation [13].
  • Development of activatable adenylate cyclase requires transcription but is independent of the fifth nuclear replication, cell division, and compaction [13].

Chemical compound and disease context of Adcy1


Biological context of Adcy1


Anatomical context of Adcy1


Associations of Adcy1 with chemical compounds

  • Adenylate cyclase inhibitor (SQ 22536), phospholipase C inhibitors (neomycin or U 73122), and protein kinase C (PKC) inhibitors (bisindolylmaleimide I or staurosporine) inhibited the ATP-induced increase in [(3)H]thymidine incorporation [25].
  • Here we show that wild-type, AC1, AC8, or AC1&8 double knockout (DKO) mice were indistinguishable in tests of acute pain, whereas behavioral responses to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant, were reduced or abolished in AC1&8 DKO mice [26].
  • Spatiotemporal localization of the calcium-stimulated adenylate cyclases, AC1 and AC8, during mouse brain development [19].
  • Here, we report that genetic deletion of AC1 significantly attenuated neuronal death induced by glutamate in primary cultures of cortical neurons, whereas AC8 deletion did not produce a significant effect [2].
  • To explore the possible roles of AC1 in cell death in vivo, we studied neuronal excitotoxicity induced by an intracortical injection of NMDA [2].

Physical interactions of Adcy1


Enzymatic interactions of Adcy1


Regulatory relationships of Adcy1


Other interactions of Adcy1

  • Therefore, we conducted the present work to test the role of AC1 and AC8 in both acute persistent and chronic muscle pain [24].
  • It is hypothesized that Ca2+ stimulation of calmodulin (CaM)-activated adenylyl cyclases (AC1 or AC8) generates cAMP signals critical for late phase LTP (L-LTP) and long-term memory (LTM) [38].
  • Capacitative Ca(2+) entry stimulates cAMP synthesis in mouse parotid acini, suggesting that one of the Ca(2+)-sensitive adenylyl cyclases (AC1 or AC8) may play an important role in the regulation of parotid function (Watson, E. L., Wu, Z., Jacobson, K. L., Storm, D. R., Singh, J. C., and Ott, S. M. (1998) Am. J. Physiol. 274, C557-C565) [39].
  • Video microscopic analyses show that AC1(brl/brl) axons have modified responses to ephrin-A5: the collapse of the growth cones occurs, but the rearward movement of the axon is arrested [40].
  • Moreover, this lack of responsiveness is accompanied by markedly reduced stimulation of adenylate cyclase in cardiac membranes from beta 1-AR -/- mice [41].

Analytical, diagnostic and therapeutic context of Adcy1

  • In the present study, Northern blot analysis shows that the ETn insertion results in loss of the normal Adcy1 transcript, a finding consistent with the loss-of-function Adcy1brl mutation, and generation of shorter transcripts [18].
  • To determine the potential role of other AC isoforms we localized the Adcy genes in the visual centres during development, using in situ hybridization [22].
  • Electroretinography (ERG) of adult Adcy1(brl) mutant mice, which are deficient in adenylyl cyclase type 1 (AC1) activity, revealed decreased amplitude of the oscillatory potentials (OP) and of the primary rising phase of the b-wave intensity-response function in scotopic conditions [42].
  • The effects of AC1 loss of function in the retina are mimicked by the blockade of ephrin-A5 signaling in WT cocultures [40].
  • Mice lacking either AC1 or AC8 genes or DKO did not differ from wild-type mice in short-term antinociceptive responses to morphine measured in the tail-flick analgesia assay [43].


  1. Calcium-stimulated adenylyl cyclases modulate ethanol-induced neurodegeneration in the neonatal brain. Maas, J.W., Indacochea, R.A., Muglia, L.M., Tran, T.T., Vogt, S.K., West, T., Benz, A., Shute, A.A., Holtzman, D.M., Mennerick, S., Olney, J.W., Muglia, L.J. J. Neurosci. (2005) [Pubmed]
  2. Genetic Evidence for Adenylyl Cyclase 1 as a Target for Preventing Neuronal Excitotoxicity Mediated by N-Methyl-D-aspartate Receptors. Wang, H., Gong, B., Vadakkan, K.I., Toyoda, H., Kaang, B.K., Zhuo, M. J. Biol. Chem. (2007) [Pubmed]
  3. Localization of adenylyl cyclase proteins in the rodent retina. Abdel-Majid, R.M., Tremblay, F., Baldridge, W.H. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  4. A nucleotide regulatory site for somatostatin inhibition of adenylate cyclase in S49 lymphoma cells. Jakobs, K.H., Aktories, K., Schultz, G. Nature (1983) [Pubmed]
  5. Experimental metastasis correlates with cyclic AMP accumulation in B16 melanoma clones. Sheppard, J.R., Koestler, T.P., Corwin, S.P., Buscarino, C., Doll, J., Lester, B., Greig, R.G., Poste, G. Nature (1984) [Pubmed]
  6. Altered activation by calcitonin and inhibition by somatostatin of human embryonal carcinoma cell adenylate cyclase with retinoic acid-induced differentiation. Liapi, C., Anderson, W.B., Evain-Brion, D. Dev. Biol. (1986) [Pubmed]
  7. Distinctive and synergistic signaling of human adenosine A2a and dopamine D2L receptors in CHO cells. Tang, Y., Demarest, K.T. J. Recept. Signal Transduct. Res. (2005) [Pubmed]
  8. Depressant effect of forskolin on spontaneous locomotor activity in mice. Barraco, R.A., Phillis, J.W., Altman, H.J. Gen. Pharmacol. (1985) [Pubmed]
  9. Biochemical, functional and behavioral evaluation of a series of novel antipsychotic-like agents. Von Voigtlander, P.F., Lahti, R.A., Tang, A.H., Sethy, V.H. Archives internationales de pharmacodynamie et de thérapie. (1983) [Pubmed]
  10. Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory cortex. Abdel-Majid, R.M., Leong, W.L., Schalkwyk, L.C., Smallman, D.S., Wong, S.T., Storm, D.R., Fine, A., Dobson, M.J., Guernsey, D.L., Neumann, P.E. Nat. Genet. (1998) [Pubmed]
  11. Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Timpl, P., Spanagel, R., Sillaber, I., Kresse, A., Reul, J.M., Stalla, G.K., Blanquet, V., Steckler, T., Holsboer, F., Wurst, W. Nat. Genet. (1998) [Pubmed]
  12. Increased expression of the c-fos proto-oncogene in bone from patients with fibrous dysplasia. Candeliere, G.A., Glorieux, F.H., Prud'homme, J., St-Arnaud, R. N. Engl. J. Med. (1995) [Pubmed]
  13. Development of activatable adenylate cyclase in the preimplantation mouse embryo and a role for cyclic AMP in blastocoel formation. Manejwala, F., Kaji, E., Schultz, R.M. Cell (1986) [Pubmed]
  14. Selection of a variant lymphoma cell deficient in adenylate cyclase. Bourne, H.R., Coffino, P., Tomkins, G.M. Science (1975) [Pubmed]
  15. An adenylate cyclase of brain reflects propensity for breast cancer in mice. Cotzias, G.C., Tang, L.C. Science (1977) [Pubmed]
  16. The adenylate cyclase toxin of Bordetella pertussis binds to target cells via the alpha(M)beta(2) integrin (CD11b/CD18). Guermonprez, P., Khelef, N., Blouin, E., Rieu, P., Ricciardi-Castagnoli, P., Guiso, N., Ladant, D., Leclerc, C. J. Exp. Med. (2001) [Pubmed]
  17. beta-Adrenergic receptors in pediatric tumors: uncoupled beta 1-adrenergic receptor in Ewing's sarcoma. Whitsett, J.A., Burdsall, J., Workman, L., Hollinger, B., Neely, J. J. Natl. Cancer Inst. (1983) [Pubmed]
  18. ETn insertion in the mouse Adcy1 gene: transcriptional and phylogenetic analyses. Leong, W.L., Dobson, M.J., Logsdon, J.M., Abdel-Majid, R.M., Schalkwyk, L.C., Guernsey, D.L., Neumann, P.E. Mamm. Genome (2000) [Pubmed]
  19. Spatiotemporal localization of the calcium-stimulated adenylate cyclases, AC1 and AC8, during mouse brain development. Nicol, X., Muzerelle, A., Bachy, I., Ravary, A., Gaspar, P. J. Comp. Neurol. (2005) [Pubmed]
  20. Role of efficient neurotransmitter release in barrel map development. Lu, H.C., Butts, D.A., Kaeser, P.S., She, W.C., Janz, R., Crair, M.C. J. Neurosci. (2006) [Pubmed]
  21. Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation. Wang, H., Pineda, V.V., Chan, G.C., Wong, S.T., Muglia, L.J., Storm, D.R. J. Neurosci. (2003) [Pubmed]
  22. Role of the calcium modulated cyclases in the development of the retinal projections. Nicol, X., Bennis, M., Ishikawa, Y., Chan, G.C., Repérant, J., Storm, D.R., Gaspar, P. Eur. J. Neurosci. (2006) [Pubmed]
  23. Adenylate cyclase 1 as a key actor in the refinement of retinal projection maps. Ravary, A., Muzerelle, A., Hervé, D., Pascoli, V., Ba-Charvet, K.N., Girault, J.A., Welker, E., Gaspar, P. J. Neurosci. (2003) [Pubmed]
  24. Genetic reduction of chronic muscle pain in mice lacking calcium/calmodulin-stimulated adenylyl cyclases. Vadakkan, K.I., Wang, H., Ko, S.W., Zastepa, E., Petrovic, M.J., Sluka, K.A., Zhuo, M. Molecular pain [electronic resource] (2006) [Pubmed]
  25. ATP Stimulates Mouse Embryonic Stem Cell Proliferation via Protein Kinase C, Phosphatidylinositol 3-Kinase/Akt, and Mitogen-Activated Protein Kinase Signaling Pathways. Heo, J.S., Han, H.J. Stem Cells (2006) [Pubmed]
  26. Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. Wei, F., Qiu, C.S., Kim, S.J., Muglia, L., Maas, J.W., Pineda, V.V., Xu, H.M., Chen, Z.F., Storm, D.R., Muglia, L.J., Zhuo, M. Neuron (2002) [Pubmed]
  27. Parathyroid hormone-related peptide as an endogenous inducer of parietal endoderm differentiation. van de Stolpe, A., Karperien, M., Löwik, C.W., Jüppner, H., Segre, G.V., Abou-Samra, A.B., de Laat, S.W., Defize, L.H. J. Cell Biol. (1993) [Pubmed]
  28. Receptor-mediated internalization is critical for the inhibition of the expression of growth hormone by somatostatin in the pituitary cell line AtT-20. Sarret, P., Nouel, D., Dal Farra, C., Vincent, J.P., Beaudet, A., Mazella, J. J. Biol. Chem. (1999) [Pubmed]
  29. Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. Dumuis, A., Sebben, M., Bockaert, J. Mol. Pharmacol. (1988) [Pubmed]
  30. Vasoactive intestinal polypeptide receptors linked to an adenylate cyclase, and their relationship with biogenic amine- and somatostatin-sensitive adenylate cyclases on central neuronal and glial cells in primary cultures. Chneiweiss, H., Glowinski, J., Prémont, J. J. Neurochem. (1985) [Pubmed]
  31. Targeted oncogenesis in the thyroid of transgenic mice. Feunteun, J., Michiels, F., Rochefort, P., Caillou, B., Talbot, M., Fournes, B., Mercken, L., Schlumberger, M., Monier, R. Horm. Res. (1997) [Pubmed]
  32. Somatostatin induces translocation of the beta-adrenergic receptor kinase and desensitizes somatostatin receptors in S49 lymphoma cells. Mayor, F., Benovic, J.L., Caron, M.G., Lefkowitz, R.J. J. Biol. Chem. (1987) [Pubmed]
  33. Mechanism of inhibition of adenylate cyclase by phospholipase C-catalyzed hydrolysis of phosphatidylcholine. Involvement of a pertussis toxin-sensitive G protein and protein kinase C. Diaz-Laviada, I., Larrodera, P., Nieto, J.L., Cornet, M.E., Diaz-Meco, M.T., Sanchez, M.J., Guddal, P.H., Johansen, T., Haro, A., Moscat, J. J. Biol. Chem. (1991) [Pubmed]
  34. Somatostatin inhibits corticotropin-releasing factor-stimulated adrenocorticotropin release, adenylate cyclase, and activation of adenosine 3',5'-monophosphate-dependent protein kinase isoenzymes in AtT20 cells. Litvin, Y., Leiser, M., Fleischer, N., Erlichman, J. Endocrinology (1986) [Pubmed]
  35. Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture. Akiyama, M., Minami, Y., Nakajima, T., Moriya, T., Shibata, S. J. Neurochem. (2001) [Pubmed]
  36. Pituitary adenylate cyclase-activating polypeptide induces cAMP production independently from vasoactive intestinal polypeptide in osteoblast-like cells. Suzuki, A., Kotoyori, J., Oiso, Y., Kozawa, O. Cell. Signal. (1994) [Pubmed]
  37. In vitro proliferation of murine spleen cells: inhibition by monoclonal antibodies to L3T4 and Lyt-2 T cell markers or intracellular cyclic adenosine monophosphate. Zhou, P., Gorzynski, T., Dowjat, W.K., Rabin, R., Zaleski, M.B. Exp. Cell Biol. (1989) [Pubmed]
  38. Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP. Wong, S.T., Athos, J., Figueroa, X.A., Pineda, V.V., Schaefer, M.L., Chavkin, C.C., Muglia, L.J., Storm, D.R. Neuron (1999) [Pubmed]
  39. The type 8 adenylyl cyclase is critical for Ca2+ stimulation of cAMP accumulation in mouse parotid acini. Watson, E.L., Jacobson, K.L., Singh, J.C., Idzerda, R., Ott, S.M., DiJulio, D.H., Wong, S.T., Storm, D.R. J. Biol. Chem. (2000) [Pubmed]
  40. Requirement of adenylate cyclase 1 for the ephrin-A5-dependent retraction of exuberant retinal axons. Nicol, X., Muzerelle, A., Rio, J.P., Métin, C., Gaspar, P. J. Neurosci. (2006) [Pubmed]
  41. Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects. Rohrer, D.K., Desai, K.H., Jasper, J.R., Stevens, M.E., Regula, D.P., Barsh, G.S., Bernstein, D., Kobilka, B.K. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  42. Electroretinographic oscillatory potentials are reduced in adenylyl cyclase type I deficient mice. Tremblay, F., Abdel-Majid, R., Neumann, P.E. Vision Res. (2002) [Pubmed]
  43. Calmodulin-stimulated adenylyl cyclase gene deletion affects morphine responses. Li, S., Lee, M.L., Bruchas, M.R., Chan, G.C., Storm, D.R., Chavkin, C. Mol. Pharmacol. (2006) [Pubmed]
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