Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 25:13:953903.
doi: 10.3389/fphar.2022.953903. eCollection 2022.

Strategies to safely target widely expressed soluble adenylyl cyclase for contraception

Jacob Ferreira  1 , Lonny R Levin  1 , Jochen Buck  1
Affiliations

Strategies to safely target widely expressed soluble adenylyl cyclase for contraception

Jacob Ferreira et al. Front Pharmacol. .

Abstract

In humans, the prototypical second messenger cyclic AMP is produced by 10 adenylyl cyclase isoforms, which are divided into two classes. Nine isoforms are G protein coupled transmembrane adenylyl cyclases (tmACs; ADCY1-9) and the 10th is the bicarbonate regulated soluble adenylyl cyclase (sAC; ADCY10). This review details why sAC is uniquely druggable and outlines ways to target sAC for novel forms of male and female contraception.

Keywords: adcy10; birth control; cAMP; capacitation; fertility; sperm motility.

PubMed Disclaimer

Conflict of interest statement

JB and LL licensed a panel of monoclonal antibodies directed against mammalian sAC to Millipore. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Two sources of cAMP in mammalian cells. ADCY1-9 are transmembrane adenylyl cyclases (tmACs) regulated by G-proteins. ADCY10 is soluble adenylyl cyclase (sAC) regulated by HCO3 − and Ca2+ ions. Phosphodiesterases (PDEs) degrade cAMP. sAC and tmACs both produce cAMP which has distinct roles.
FIGURE 2
FIGURE 2
Different isoforms of sAC with catalytic and functional domains highlighted. sACt and sACfl are present in testis and sperm, while sACsomatic appears to be ubiquitously expressed.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Acin-Perez R., Salazar E., Kamenetsky M., Buck J., Levin L. R., Manfredi G. (2009). Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation. Cell Metab. 9, 265–276. 10.1016/j.cmet.2009.01.012 - DOI - PMC - PubMed
    1. Akbari A., Pipitone G. B., Anvar Z., Jaafarinia M., Ferrari M., Carrera P., et al. (2019). ADCY10 frameshift variant leading to severe recessive asthenozoospermia and segregating with absorptive hypercalciuria. Hum. Reprod. 34, 1155–1164. 10.1093/humrep/dez048 - DOI - PubMed
    1. Amory J. K. (2016). Male contraception. Fertil. Steril. 106, 1303–1309. 10.1016/j.fertnstert.2016.08.036 - DOI - PMC - PubMed
    1. Austin C. R. (1951). Activation and the correlation between male and female elements in fertilization. Nature 168, 558–559. 10.1038/168558c0 - DOI - PubMed
    1. Baillie G. S., Tejeda G. S., Kelly M. P. (2019). Therapeutic targeting of 3', 5'-cyclic nucleotide phosphodiesterases: Inhibition and beyond. Nat. Rev. Drug Discov. 18, 770–796. 10.1038/s41573-019-0033-4 - DOI - PMC - PubMed

LinkOut - more resources