Forskolin increases cellular cyclic adenosine monophosphate content and parathyroid hormone release in dispersed bovine parathyroid cells

Abstract

We studied the effects of the positive-inotropic and hypotensive agent forskolin on parathyroid hormone (PTH) release, cAMP accumulation, and adenylate cyclase activity in dispersed bovine parathyroid cells. Forskolin stimulated PTH release 1.7 to 3.7-fold at 10 −5 mol/L and increased cAMP content maximally 37.6-fold at 10 −4 mol/L. Forskolin induced a maximal increase in cAMP accumulation by 5 minutes of incubation. The rate of PTH release in forskolin-treated cells also reached maximal levels at five to ten minutes incubation. There was a dose-dependent increase in PTH release and cAMP content over the range of 10 −7 to 10 −4 M forskolin with half-maximal stimulation at 10 −7 to 10 −6 mol/L for PTH release and between 10 −5 and 10 −4 mol/L for cAMP content. PTH release and cAMP accumulation were inhibited by increasing extracellular calcium concentrations in both control cells and those incubated with 10 −5 mol/L forskolin. Forskolin stimulated adenylate cyclase activity in lysates from parathyroid cells 15.7-fold with half-maximal activation between 10 −6 and 10 −5 mol/L forskolin. Forskolin-stimulated (10 −5 mol/L) and basal adenylate cyclase activities declined in parallel with increasing calcium concentrations. In contrast, phosphodiesterase activity was unaffected by forskolin at 10 −6 to 10 −4 mol/L. Forskolin, therefore, by directly activating adenylate cyclase, enhances cAMP accumulation and PTH release in dispersed bovine parathyroid cells. As with other agents activating cAMP accumulation in this system, these effects are inhibited by elevated calcium concentrations. Thus, the activation of PTH secretion by cAMP and the modulation of these processes by calcium are independent of the locus at which the increase in cAMP takes place.