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Gene Review

Adcy8  -  adenylate cyclase 8

Mus musculus

Synonyms: AC8, ATP pyrophosphate-lyase 8, AW060868, Adenylate cyclase type 8, Adenylate cyclase type VIII, ...
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Psychiatry related information on Adcy8

  • ABSTRACT : BACKGROUND : The Ca2+/calmodulin-stimulated adenylyl cyclase (AC) isoforms AC1 and AC8, couple NMDA receptor activation to cAMP signaling pathways in neurons and are important for development, learning and memory, drug addiction and persistent pain [1].

High impact information on Adcy8

  • 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 [2].
  • AC1 and AC8 are highly expressed in the anterior cingulate cortex (ACC), and contribute to inflammation-induced activation of CREB [2].
  • By generating transgenic mice whose expression of beta-galactosidase is controlled by the AC8 5'-flanking DNA sequences, we demonstrate that the DNA sequences within the 10 kb preceding exon 1 are critical for establishment of this region-specific pattern [3].
  • By in situ hybridization, we have found the highest expression of AC8 mRNA within the olfactory bulb, thalamus, habenula, cerebral cortex, and hypothalamic supraoptic and paraventricular nuclei [3].
  • A cloned, virus-producing, tumorigenic, promonocytic leukemia cell line, AC8, derived from an Abelson murine leukemia virus-infected mouse can differentiate in vitro [4].

Biological context of Adcy8

  • AC8 gene expression also begins early in embryonic life (E12)--but in a more limited number of regions than in adults [5].
  • Here, we have used the N terminus of AC8 as a bait in a yeast two-hybrid screen of a human embryonic kidney (HEK) 293 cell cDNA library and identified the catalytic subunit of the serine/threonine protein phosphatase 2A (PP2A(C)) as a binding partner [6].
  • PKA-mediated phosphorylation did not influence either calmodulin or PP2A(C) association with AC8 [6].
  • AC8 transgenic mice thus represent an original model to investigate the relative influence of Ca(2+) and cAMP on cardiac function within a phenotype of enhanced cardiac contractility and relaxation [7].

Anatomical context of Adcy8


Associations of Adcy8 with chemical compounds

  • 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 [8].
  • Cortical lesions induced by NMDA were significantly reduced in AC1 but not in AC8 knock-out mice [8].
  • Spatiotemporal localization of the calcium-stimulated adenylate cyclases, AC1 and AC8, during mouse brain development [5].
  • Seemingly, a protein, glycoprotein, and carbohydrate were recognized by MAB E6, FE10, and AC8, respectively [11].
  • Cyclic AMP compartmentation due to increased cAMP-phosphodiesterase activity in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8) [12].

Other interactions of Adcy8

  • Therefore, we conducted the present work to test the role of AC1 and AC8 in both acute persistent and chronic muscle pain [1].
  • Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement [13].
  • Of particular interest were AC3 and AC8, located in the same regions as, and hence possibly directly associated with, specific cell surface receptors and G proteins that are able to regulate the spermatozoon's acquisition and maintenance of fertilizing ability via changes in AC/cAMP [14].
  • In contrast, AC8 KO and DKO mice, but not AC1 KO mice, demonstrate decreased voluntary ethanol consumption compared with WT mice [15].

Analytical, diagnostic and therapeutic context of Adcy8

  • 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 [16].


  1. 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]
  2. 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]
  3. The 5'-flanking region of the mouse adenylyl cyclase type VIII gene imparts tissue-specific expression in transgenic mice. Muglia, L.M., Schaefer, M.L., Vogt, S.K., Gurtner, G., Imamura, A., Muglia, L.J. J. Neurosci. (1999) [Pubmed]
  4. Viral oncogene expression during differentiation of Abelson virus-infected murine promonocytic leukemia cells. Hines, D.L. Cancer Res. (1988) [Pubmed]
  5. 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]
  6. A direct interaction between the N terminus of adenylyl cyclase AC8 and the catalytic subunit of protein phosphatase 2A. Crossthwaite, A.J., Ciruela, A., Rayner, T.F., Cooper, D.M. Mol. Pharmacol. (2006) [Pubmed]
  7. Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase. Lipskaia, L., Defer, N., Esposito, G., Hajar, I., Garel, M.C., Rockman, H.A., Hanoune, J. Circ. Res. (2000) [Pubmed]
  8. 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]
  9. 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]
  10. 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]
  11. Production and preliminary characterization of murine monoclonal antibodies to Ichthyophthirius multifiliis, a protozoan parasite of fish. Dickerson, H.W., Evans, D.L., Gratzek, J.B. Am. J. Vet. Res. (1986) [Pubmed]
  12. Cyclic AMP compartmentation due to increased cAMP-phosphodiesterase activity in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8). Georget, M., Mateo, P., Vandecasteele, G., Lipskaia, L., Defer, N., Hanoune, J., Hoerter, J., Lugnier, C., Fischmeister, R. FASEB J. (2003) [Pubmed]
  13. Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons. Wang, G.D., Zhuo, M. J. Neurophysiol. (2002) [Pubmed]
  14. Evidence for multiple distinctly localized adenylyl cyclase isoforms in mammalian spermatozoa. Baxendale, R.W., Fraser, L.R. Mol. Reprod. Dev. (2003) [Pubmed]
  15. Calcium-stimulated adenylyl cyclases are critical modulators of neuronal ethanol sensitivity. Maas, J.W., Vogt, S.K., Chan, G.C., Pineda, V.V., Storm, D.R., Muglia, L.J. J. Neurosci. (2005) [Pubmed]
  16. 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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