STIMULATION OF THE TYPE-III OLFACTORY ADENYLYL CYCLASE BY CALCIUM AND CALMODULIN

被引:216
作者
CHOI, EJ [1 ]
XIA, ZG [1 ]
STORM, DR [1 ]
机构
[1] UNIV WASHINGTON, DEPT PHARMACOL, SEATTLE, WA 98195 USA
关键词
D O I
10.1021/bi00143a019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 adenylyl cyclase 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-mu-M 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 frec Ca2+ accompanying receptor activation may amplify the primary cyclic AMP signal.
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页码:6492 / 6498
页数:7
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