Inhibition of protein phosphatase 1 decreases PTH secretion from isolated dispersed parathyroid cells

To investigate the regulation of parathyroid hormone secretion by phosphata ses we examined the effect of okadaic acid, a selective inhibitor of protei n phosphatases (PP)-1 and -2A, on isolated, dispersed parathyroid cells. Ok adaic acid inhibited secretion from intact bovine, intact human and strepto lysin-O permeabilized bovine cells. Approximately 10(-6) M okadaic acid res ulted in a 50% decrease in parathyroid hormone (PTH) secretion from both in tact and permeabilized cells, consistent with PP-1 being the target of inhi bition. Upon subcellular fractionation, PP-1 overlapped but was not identic al to either PTH, a marker of the secretory granule, or Na+/K+-ATPase, a pl asma membrane marker. In summary, PP-1 activity is involved in Ca2+-depende nt but not basal PTH secretion. (C) 1999 Published by Elsevier Science Irel and Ltd. All rights reserved.