Cholera Toxin Stimulates 3',5'-Adenosine Monophosphate Accumulation and Parathyroid Hormone Release from Dispersed Bovine Parathyroid Cells**

Abstract

The effects of cholera toxin on cAMP accumulation and parathyroid hormone (PTH) release were investigated in dispersed bovine parathyroid cells. Incubation with toxin resulted in a 5- to 10-fold rise in intracellular cAMP after a lag of 50–60 min, which correlated closely with 40–60% stimulation of PTH release. These responses exhibited a dose-dependent relationship to cholera toxin concentration over a range of 10^-11-10^-9 M with half-maximal stimulation of both cyclic nucleotide accumulation and hormone release occurring at 3–5 × 10^-11 M toxin. Cholera toxin also affected the stimulation due to other agonists known to interact with this system. The maximal activation of cAMP accumulation by isoproterenol or dopamine was augmented relatively little after preincubation with toxin for 90 min, but the apparent KA (concentration for agonist causing 50% of maximal cAMP accumulation) for agonists was decreased 4- to 10-fold. The KA for secretin, which normally causes relatively small increases in cAMP accumulation, was also decreased by 3- to 4-fold, but in addition, cholera toxin pretreatment increased maximal secretin-stimulated cAMP accumulation by 4- to 8-fold. An analogous decrease in KA was observed for stimulation of PTH release by dopamine and secretin. On the other hand, the actions of a-adrenergic agonists and prostaglandin F2O, which normally inhibit cAMP accumulation, were unaffected by toxin. These results showed that cholera toxin increases both cAMP accumulation and PTH release from dispersed parathyroid cells, again confirming the close relationship between cAMP and its biological effects in this system. In addition, cholera toxin seemed to render dispersed parathyroid cells more sensitive to other agonists known to stimulate this cell type and may be a useful agent for further study of these and other as yet unidentified secretagogues.