Functional properties of Ca2+-inhibitable type 5 and type 6 adenylyl cyclases and role of Ca2+ increase in the inhibition of intracellular cAMP content

Cell Signal. 1999 Sep;11(9):651-63. doi: 10.1016/s0898-6568(99)00031-5.


Among the different adenylyl cyclase (AC) isoforms, type 5 and type 6 constitute a subfamily which has the remarkable property of being inhibited by submicromolar Ca2+ concentrations in addition to Galphai-mediated processes. These independent and cumulative negative regulations are associated to a low basal enzymatic activity which can be strongly activated by Galphas-mediated interactions or forskolin. These properties ensure possible wide changes of cAMP synthesis. Regulation of cAMP synthesis by Ca2+ was studied in cultured or native cells which express naturally type 5 and/or type 6 AC, including well-defined renal epithelial cells. The results underline two characteristics of the inhibition due to agonist-elicited increase of intracellular Ca2+: i) Ca2+ rises achieved through capacitive Ca2+ entry or intracellular Ca2+ release can inhibit AC to a similar extent; and ii) in a same cell type, different agonists inducing similar overall Ca2+ rises elicit a variable inhibition of AC activity. The results suggest that a high efficiency of AC regulation by Ca2+ is linked to a requisite close localization of AC enzyme and Ca2+ rises.

Publication types

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

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / physiology*
  • Animals
  • Calcium / metabolism
  • Calcium / physiology*
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / metabolism*
  • Humans
  • Intracellular Fluid
  • Isoenzymes / physiology


  • Adenylyl Cyclase Inhibitors
  • Isoenzymes
  • Cyclic AMP
  • Adenylyl Cyclases
  • Calcium