Effects of pertussis toxin on adenylate cyclase responses to prostaglandin E2 and calcitonin in human breast cancer cells

Publisher Website
Google Scholar
Abstract
Both calcitonin and prostaglandin E2 (PGE2) stimulate adenylate cyclase activity in the human breast cancer cell line (T 47D). The maximum cAMP response to calcitonin exceeds that of PGE2. When maximal concentrations of the 2 hormones were added simultaneously to the cells, the amount of cAMP generated was less than that seen with calcitonin alone. When cells were treated with the protein toxin of Bordetella pertussis (islet-activating protein; IAP) which inactivates the inhibitory regulatory component (Ni) of adenylate cyclase, there was no change in basal or calcitonin-responsive adenylate cyclase in intact cells. The PGE2 response was augmented at all dose levels, and this effect was dependent on the concentration of IAP. In cells pretreated with IAP, simultaneous addition of PGE2 and calcitonin resulted in additivity rather than in inhibition of cAMP production. The additivity of the response to calcitonin and PGE2 after IAP treatment implies activation of separate pools of adenylate cyclase catalytic subunit by the 2 hormones. These data are consistent with a model in which calcitonin acts on adenylate cyclase in T 47D cells through stimulatory regulatory components alone; PGE2 acts on the same cells through both stimulatory and inhibitory components. The Ni input can limit the maximum effect of PGE2 and is capable of limiting calcitonin effects when the 2 agonists are used simultaneously.