ROLE OF CALCIUM CHANNELS IN PARATHYROID-HORMONE SECRETION

Experimental evidence exists for the presence of parathyroid cell. mem brane calcium channels that respond to plasma calcium, In previous rep orts, the effects of various calcium channel agents on PTH secretion h ave revealed conflicting results, To resolve some of these inconsisten cies, we have compared the pure calcium channel agonist, (+)202-791, a nd its antagonistic enantiomer (-)202-791 with other calcium channel a gents-verapamil, nifedipine, and (+)Bay-K-8644. The agonist (+)202-791 enhanced Ca-45(+2) uptake and decreased PTH secretion, while the anta gonist (-)202-791 decreased Ca-45(+2) uptake and increased PTH secreti on, The calcium channel appears coupled to a G-protein as indicated by pertussis toxin treatment of the cells, The enantiomers (+/-)202-791. had little effect on intracellular cAMP production suggesting that th e calcium channel may not be responsible for the previously observed c alcium-mediated changes in cAMP, The antagonist (-)202-791 increased t he phosphorylation of a 60-kd protein, The enantiomers (+/-)202-791 di d not alter the effect of depolarizing concentrations of potassium on PTH secretion, Our results suggest that calcium channels provide a pat hway for the movement of calcium across the plasma membrane and that t his pool of calcium regulates, at least in part, PTH secretion.