Effects of the antihypercalcemic drugs gallium nitrate and pamidronate on hormone release of pathologic human parathyroid cells.
BACKGROUND
Gallium nitrate and the bisphosphonates pamidronate and its dimethylated derivative comprise antihypercalcemic drugs with actions on bone. This study examines the in vitro effects of these compounds on human parathyroid cells.


METHODS
Parathyroid hormone (PTH) release and the concentration of cytoplasmic calcium ion (Ca2+) of dispersed cells from parathyroid glands of 27 patients with sporadic primary or uremic hyperparathyroidism was measured.


RESULTS
In 1.25 mmol/L external Ca2+, 200 mumol/L gallium nitrate inhibited PTH release from preparations of primary and uremic hyperparathyroidism by 14% and 22%, respectively. Similar reductions were evident also in 0.5 and 3.0 mmol/L Ca2+. The gallium nitrate-induced suppression of PTH release was dose dependent in the 2 to 200 mumol/L range. Cytoplasmic Ca2+ concentration displayed a biphasic rise on elevation of external Ca2+ and remained unaffected by gallium nitrate. None of the bisphosphonates altered PTH release of pathologic human or normal bovine parathyroid cells.


CONCLUSIONS
The results support clinical usefulness of gallium nitrate through its dual actions on bone and the parathyroid. The findings substantiate that gallium may reduce PTH release by stabilization of the plasma membrane rather than by interference with the surface cation receptor mediating Ca2+ regulation of the secretion.
Ridefelt
P
P
Department of Surgery, University of Uppsala, Sweden.
Gylfe
E
E
Akerström
G
G
Rastad
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D005708:Gallium / Q000494:pharmacology*; D006801:Humans; D006934:Hypercalcemia / Q000378:metabolism* / Q000473:pathology; D006961:Hyperparathyroidism / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D008875:Middle Aged; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D004164:Diphosphonates; D010281:Parathyroid Hormone; D005708:Gallium; D000077268:Pamidronate; D002118:Calcium; C027235:gallium nitrate