Inhibition of protein phosphatase 1 decreases PTH secretion from isolated dispersed parathyroid cells.
To investigate the regulation of parathyroid hormone secretion by phosphatases we examined the effect of okadaic acid, a selective inhibitor of protein phosphatases (PP)-1 and -2A, on isolated, dispersed parathyroid cells. Okadaic acid inhibited secretion from intact bovine, intact human and streptolysin-O permeabilized bovine cells. Approximately 10(-6) M okadaic acid resulted in a 50% decrease in parathyroid hormone (PTH) secretion from both intact and permeabilized cells, consistent with PP-1 being the target of inhibition. Upon subcellular fractionation, PP-1 overlapped but was not identical to either PTH, a marker of the secretory granule, or Na+/K+-ATPase, a plasma membrane marker. In summary, PP-1 activity is involved in Ca2+-dependent but not basal PTH secretion.
Matovcik
L M
LM
VA Connecticut Healthcare System, and the Department of Surgery, Yale University School of Medicine, New Haven 06520-8062, USA. matovcik@aol.com
Rhee
S S
SS
Schaefer
J F
JF
da Cruz e Silva
E F
EF
Kinder
B K
BK
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D006801:Humans; D019319:Okadaic Acid / Q000494:pharmacology; D010280:Parathyroid Glands / Q000166:cytology* / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D054645:Protein Phosphatase 1; D013301:Streptolysins / Q000494:pharmacology; D013347:Subcellular Fractions / Q000737:chemistry
D010281:Parathyroid Hormone; D013301:Streptolysins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D002118:Calcium