Fig. 2.

Cyclase-specific reagents to study sources of cAMP in mammalian cells. Selective activators and inhibitors provide tools to distinguish the relative contributions of tmACs and sAC to cAMP signaling. L refers to ligand of G protein-coupled receptor; Gα-GDP and Gα-GTP refer to the inactive and active forms of the α-subunit of heterotrimeric G protein; C1a and C2a refer the two catalytic domains of tmACs; CE refers to catechol derivatives of estrogen, such as 2- or 4-hydroxyestradiol, which inhibit sAC (and related enzymes) by chelating the magnesium ion in the enzyme's active site (52). KH7 is a specific sAC inhibitor, which works via an unknown mechanism, identified in a small molecule screen (29).