Parathyroid hormone controls the size of the intracellular Ca2+ stores available to receptors linked to inositol trisphosphate formation

In HEK 293 cells stably expressing type 1 parathyroid (PTH) receptors, PTH stimulated release of intracellular Ca2+ stores in only 27% of cells, where as 96% of cells responded to carbachol, However, in almost all cells PTH po tentiated the response to carbachol by about 3-fold. Responses to carbachol did not desensitize, but only the first challenge in Ca2+-free medium caus ed an increase in [Ca2+](i), indicating that the carbachol-sensitive Ca2+ s tores had been emptied. Subsequent addition of PTH also failed to increase [Ca2+](i), but when it was followed by carbachol there was a substantial in crease in [Ca2+](i), A similar potentiation was observed between ATP and PT H but not between carbachol and ATP. Intracellular heparin inhibited respon ses to carbachol and PTH, and pretreatment with ATP and carbachol abolished responses to PTH, suggesting that the effects of PTH involve inositol tris phosphate (IP3) receptors, PTH neither stimulated detectable IP3 formation nor affected the amount formed in response to ATP or carbachol, PTH stimula ted cyclic AMP formation, but this was not the means whereby PTH potentiate d Ca2+ signals. We suggest that PTH may regulate Ca2+ mobilization by facil itating translocation of Ca2+ between discrete intracellular stores and tha t it thereby regulates the size of the Ca2+ pool available to receptors lin ked to IP3 formation.