cCMP, cUMP, cTMP, cIMP and cXMP as possible second messengers: development of a hypothesis based on studies with soluble guanylyl cyclase α(1)β(1)

Biol Chem. 2013 Feb;394(2):261-70. doi: 10.1515/hsz-2012-0282.


Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate are second messengers that regulate multiple physiological functions. The existence of additional cyclic nucleotides in mammalian cells was postulated many years ago, but technical problems hampered development of the field. Using highly specific and sensitive mass spectrometry methods, soluble guanylyl cyclase has recently been shown to catalyze the formation of several cyclic nucleotides in vitro. This minireview discusses the broad substrate-specificity of soluble guanylyl cyclase and the possible second messenger roles of cyclic nucleotides other than adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate. We hope that this article stimulates productive and critical research in an area that has been neglected for many years.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclic CMP / metabolism*
  • Cyclic IMP / metabolism*
  • Guanylate Cyclase / chemistry
  • Guanylate Cyclase / metabolism*
  • Humans
  • Models, Biological
  • Nucleotides, Cyclic / metabolism*
  • Purine Nucleotides / metabolism*
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Second Messenger Systems*
  • Soluble Guanylyl Cyclase
  • Thymidine Monophosphate / metabolism*
  • Uridine Monophosphate / metabolism*


  • Nucleotides, Cyclic
  • Purine Nucleotides
  • Receptors, Cytoplasmic and Nuclear
  • cyclic XMP
  • Cyclic IMP
  • Cyclic CMP
  • Thymidine Monophosphate
  • cyclic 3',5'-uridine monophosphate
  • cyclic 3',5'-thymidine monophosphate
  • Uridine Monophosphate
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase