Functional properties of Ca2+-inhibitable type 5 and type 6 adenylyl cyclases and role of Ca2+ increase in the inhibition of intracellular cAMP content.
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.
Chabardès
D
D
URA 1859 CNRS, Service de Biologie Cellulaire, Département de Biologie Cellulaire et Moléculaire, Gif sur Yvette, France. chabardes@dsvidf.cea.fr
Imbert-Teboul
M
M
Elalouf
J M
JM
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007424:Intracellular Fluid; D007527:Isoenzymes / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D007527:Isoenzymes; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium