Stimulation of the Type III Olfactory Adenylyl Cyclase by Calciumand Calmodulin

Characterization of adenylyl cyclases has been facilitated by the isolation of cDNA clones for distinct adenylyl cyclases including the type I and type III enzymes. Expression of type I adenylyl cyclase activity in animal cells has established that this enzyme is stimulated by calmodulin and Ca²⁺. Type III adenylyl cyclase is enriched in olfactory neurons and is regulated by stimulatory G proteins. The sensitivity of the type III adenylyl cyclase to Ca²⁺ and calmodulin has not been reported. In this study, type III adenylylcyclase was expressed in human kidney 293 cells to determine if the enzyme is stimulated by Ca²⁺ and calmodulin. The type III enzyme was not stimulated by Ca²⁺ and calmodulin in the absence of other effectors. It was, however, stimulated by Ca²⁺ through calmodulin when the enzyme was concomitantly activated by either GppNHp or forskolin. The concentrations of free Ca²⁺ for half-maximal stimulation of type I and type III adenylyl cyclases were 0.05 and 5.0 μM Ca²⁺, respectively. These data suggest that the type III adenylyl cyclase is stimulated by Ca²⁺ when the enzyme is activated by G-protein-coupled receptors and that increases in free Ca²⁺ accompanying receptor activation may amplify the primary cyclic AMP signal.