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Gene Review

Adcy5  -  adenylate cyclase 5

Mus musculus

Synonyms: AC5, ATP pyrophosphate-lyase 5, AW121902, Ac5, Adenylate cyclase type 5, ...
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Psychiatry related information on Adcy5

  • Here we show that all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated in mice lacking adenylyl cyclase type 5 (AC5), a form of adenylyl cyclase that is highly enriched in striatum [1].
  • However, D1- or A2A-specific pharmaco-behaviors were basically preserved, whereas the signal cascade from D2 to AC was completely abolished in AC5(-/-), and motor activity of AC5(-/-) was not suppressed by treatment of cataleptic doses of the antipsychotic drugs haloperidol and sulpiride [2].

High impact information on Adcy5

  • Together, these results establish AC5 as an important component of mu and delta opioid receptor signal transduction mechanisms in vivo and provide further support for the importance of the cAMP pathway as a critical mediator of opioid action [1].
  • The protective mechanism seems to involve Bcl-2, which was up-regulated significantly more in AC5-/- mice with pressure overload [3].
  • Left ventricular weight/tibial length ratio (LVW/TL) was not different between the WT and AC5-/- at baseline and increased progressively and similarly in both groups at 1 and 3 wk after aortic banding [3].
  • The dose-response curve for Zn(2+) inhibition was identical for AC1, AC5, and AC6 as well as for the C441R mutant of AC5 whose defect appears to be in one of the catalytic metal binding sites [4].
  • Immunoblot analysis revealed that AC5/6 and AC3 are expressed in parotid glands [5].

Biological context of Adcy5

  • The calcium paradoxon of renin release: calcium suppresses renin exocytosis by inhibition of calcium-dependent adenylate cyclases AC5 and AC6 [6].
  • Together, the results strongly suggest that 1) a rise in cyclic AMP (cAMP) may be associated with cardiomyocyte and endodermal cell differentiation during mammalian embryogenesis; and 2) AC5 gene expression starts very early during normal mouse cardiogenesis and correlates with the differentiation of cardiomyocytes [7].
  • Particularly, the marked increase in AC5 mRNA correlates with the appearance of beating cardiomyocytes and with the transcription of the atrial myosin light chain (MLC1A) gene which encodes a protein specifically involved in the cardiac muscle cell contractile phenotype [7].
  • Paradoxically, conscious AC5-/- mice had a higher heart rate compared with wild-type (WT) mice (613+/-8 versus 523+/-11 bpm, P<0.01, n=14 to 15) [8].

Anatomical context of Adcy5


Associations of Adcy5 with chemical compounds

  • Interestingly, both haloperidol and clozapine at low doses remarkably increased the locomotion of AC5(-/-) in the open field test that was produced in part by a common mechanism that involved the increased activation of D1 dopamine receptors [2].
  • Because cAMP is the main intracellular stimulator of renin release, we hypothesized that calcium might exert its suppressive effects on renin secretion via the inhibition of the calcium-regulated adenylate cyclases AC5 and AC6 [6].
  • By contrast, even the concentration range over which Ca(2+) inhibits adenylyl cyclases AC5 and AC6 is not unambiguously defined; even less so is the mechanism of inhibition [11].
  • The compound with the most interesting properties (high affinity and selectivity for the acetylcholine binding site, as well as agonist activity and high photolabeling yield) is AC5, a structural analogue of the fluorescent agonist dansyl-C6-choline, which has been previously used to characterize the different states of the nicotinic receptor [12].
  • Data suggest that NO produced endogenously has dual effects on cAMP accumulation in mouse parotid acini, an inhibitory effect on AC activity and a modulatory effect on capacitative Ca(2+) entry resulting in AC5/6 inhibition [13].

Regulatory relationships of Adcy5

  • The genetic ablation of the AC5 gene eliminated >80% of forskolin-induced AC activity and 85-90% of AC activity stimulated by either D1 or A2A receptor agonists in striatum [2].

Other interactions of Adcy5

  • No abnormalities were detectable in the AC5(-/-) or the AC8(-/-) mice [9].

Analytical, diagnostic and therapeutic context of Adcy5

  • As determined by Western blot and RT-PCR analysis, the four forskolin-resistant mutants all were deficient in AC-4; the levels of other AC isoforms (AC-1, AC-3 and AC-5/6) were comparable to the levels in parent Y1 cells [14].


  1. Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action. Kim, K.S., Lee, K.W., Lee, K.W., Im, J.Y., Yoo, J.Y., Kim, S.W., Lee, J.K., Nestler, E.J., Han, P.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase. Lee, K.W., Hong, J.H., Choi, I.Y., Che, Y., Lee, J.K., Yang, S.D., Song, C.W., Kang, H.S., Lee, J.H., Noh, J.S., Shin, H.S., Han, P.L. J. Neurosci. (2002) [Pubmed]
  3. Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload. Okumura, S., Takagi, G., Kawabe, J., Yang, G., Lee, M.C., Hong, C., Liu, J., Vatner, D.E., Sadoshima, J., Vatner, S.F., Ishikawa, Y. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  4. Zinc inhibition of cAMP signaling. Klein, C., Sunahara, R.K., Hudson, T.Y., Heyduk, T., Howlett, A.C. J. Biol. Chem. (2002) [Pubmed]
  5. 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]
  6. The calcium paradoxon of renin release: calcium suppresses renin exocytosis by inhibition of calcium-dependent adenylate cyclases AC5 and AC6. Gr??nberger, C., Obermayer, B., Klar, J., Kurtz, A., Schweda, F. Circ. Res. (2006) [Pubmed]
  7. Adenylyl cyclase activity and gene expression during mesodermal differentiation of the P19 embryonal carcinoma cells. Lipskaia, L., Grépin, C., Defer, N., Hanoune, J. J. Cell. Physiol. (1998) [Pubmed]
  8. Type 5 adenylyl cyclase disruption alters not only sympathetic but also parasympathetic and calcium-mediated cardiac regulation. Okumura, S., Kawabe, J., Yatani, A., Takagi, G., Lee, M.C., Hong, C., Liu, J., Takagi, I., Sadoshima, J., Vatner, D.E., Vatner, S.F., Ishikawa, Y. Circ. Res. (2003) [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. Nitric oxide inhibitable isoforms of adenylate cyclase mediate epithelial secretory dysfunction following exposure to ionising radiation. Freeman, S.L., MacNaughton, W.K. Gut (2004) [Pubmed]
  11. Inhibition by calcium of mammalian adenylyl cyclases. Guillou, J.L., Nakata, H., Cooper, D.M. J. Biol. Chem. (1999) [Pubmed]
  12. Photoactivatable agonist of the nicotinic acetylcholine receptor: potential probe to characterize the structural transitions of the acetylcholine binding site in different states of the receptor. Chatrenet, B., Kotzba-Hibert, F., Mulle, C., Changeux, J.P., Goeldner, M.P., Hirth, C. Mol. Pharmacol. (1992) [Pubmed]
  13. Nitric oxide inhibition of cAMP synthesis in parotid acini: regulation of type 5/6 adenylyl cyclase. Watson, E.L., Singh, J.C., Jacobson, K.L., Ott, S.M. Cell. Signal. (2001) [Pubmed]
  14. Forskolin-resistant Y1 adrenal cell mutants are deficient in adenylyl cyclase type 4. Al-Hakim, A., Rui, X., Tsao, J., Albert, P.R., Schimmer, B.P. Mol. Cell. Endocrinol. (2004) [Pubmed]
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