Dual effects of a new hypocalcemic agent, WR-2721, on cytoplasmic Ca2+ and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism.
The effects of the new hypocalcemic agent, WR-2721, on calcium-regulated parathyroid hormone (PTH) release, cytoplasmic Ca2+ (Ca2+i) and membrane potential were measured in dispersed parathyroid cells from patients with hyperparathyrodisim (HPT). The drug had no effects in the absence of extracellular Ca2+ but acted synergistically with Ca2+ in the 0.5-1.5 mM range by depolarizing the cells, increasing Ca2+i and inhibiting PTH release. Although the depolarizing effect of 3.0 mM Ca2+ was unaffected by WR-2721 the drug antagonized the effect of Ca2+ by decreasing Ca2+i and stimulating PTH release. Whereas the inhibitory actions of WR-2721 on PTH release may result from the activation of the mechanism for Ca2+ gating in the parathyroid cell plasma membrane, the stimulatory effect probably reflects increased intracellular Ca2+ sequestration. The drug is considered potentially important for the treatment of HPT.
D004999:Amifostine / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D003593:Cytoplasm / Q000032:analysis*; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*
D009946:Organothiophosphorus Compounds; D010281:Parathyroid Hormone; D004999:Amifostine; D002118:Calcium