Guanosine 5′‐O‐(2‐thiodiphosphate) as a competitive inhibitor of GTP in hormone or cholera toxin‐stimulated pancreatic adenylate cyclase

The hormone-sensitive adenylate cyclase of many eucaryotic cells is controlled by the presence of guanyl nucleotides (reviewed [ 1,2]). The catalytic subunit is highly active in the presence of a guanyl nucleotide triphosphate but is inactive or poorly active in the presence of GDP [3-51. Hormones act in altering the configuration of the system to facilitate the access of the activating nucleotide triphosphate 14-71. The switch-off mechanism of adenylate cyclase activity consists of the hydrolysis of the guanyl nucleotide triphosphate by the GTPase present in the system and can be i~ibited by a cholera toxin pretreatment ]&-IO].