Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling 
molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from 
the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs). 
Mammalian sAC is distributed throughout the cytoplasm and it may be present in 
the nucleus and inside mitochondria. sAC activity is directly stimulated by 
HCO3(-), and sAC has been confirmed to be a HCO3(-) sensor in a variety of 
mammalian cell types. In addition, sAC can functionally associate with carbonic 
anhydrases to act as a de facto sensor of pH and CO2. The two catalytic domains 
of sAC are related to HCO3(-)-regulated adenylyl cyclases from cyanobacteria, 
suggesting the cAMP pathway is an evolutionarily conserved mechanism for sensing 
CO2 levels and/or acid/base conditions. Reports of sAC in aquatic animals are 
still limited but are rapidly accumulating. In shark gills, sAC senses blood 
alkalosis and triggers compensatory H(+) absorption. In the intestine of bony 
fishes, sAC modulates NaCl and water absorption. And in sea urchin sperm, sAC 
may participate in the initiation of flagellar movement and in the acrosome 
reaction. Bioinformatics and RT-PCR results reveal that sAC orthologs are 
present in most animal phyla. This review summarizes the current knowledge on 
the physiological roles of sAC in aquatic animals and suggests additional 
functions in which sAC may be involved.