NPS R-467对甲状旁腺细胞分泌甲状旁腺激素的作用

目的 观察钙受体（CaR)激动剂NPS R－467对严重继发性甲状旁腺功能亢进（SHPT）患者甲状旁腺细胞分泌甲状旁腺激素（PTH）功能的影响。方法 对严重SHPT患者手术切除的甲状旁腺组织进行细胞培养。在培养90min时加入NPS R－467及其异构体NPS S－467,后者作为阴性对照。药物的终浓度分别为25、50和100nmol/L,用放免法检测加药15、30、60min后培养上清液中PTH的分泌量。结果 加药15min后,NPS R－467组和阴性对照组PTH的分泌值非常接近,约为1．8ng/10^5细胞。随后NPS S－467组PTH的测定值呈上升趋势,加药60min后达2．3ng/10^5细胞,而PS R－467组在加药30min后降为对照组的80％,加药60min后降为对照组的60％,不同剂量组间NPS R－467的效应无明显差异。结论 CaR激动剂NPS R－467能明显抑制重症SHPT患者甲状旁腺细胞PTH的分泌,可能将成为治疗甲状旁腺功能亢进的有效药物。

Effect of NPS R-467 on PTH secretion of cultured parathyroid cells from secondary hyperparathyroidism patients

OBJECTIVE: To observe the effect of NPS R-467, a calcimimetic, on PTH secretion of cultured parathyroid cells from severe secondary hyperparathyroidism (SHPT) patient. METHODS: The parathyroid tissue from a severe SHPT patient (iPTH: 2000 pg/ml) who had underwent parathyroidectomy was cultured in medium containing 1.05 mmol/L Ca and 0.8 mmo/L Mg. After 90 minutes' culture, NPS R-467 or NPS S-467, as negative control, with the final concentrations of 25, 50, and 100 nmol/L was added. The supernatant of medium was aspirated after 15, 30, and 60 minutes and iPTH therein was measured by radioimmunoassay. RESULTS: There was no difference between the PTH concentrations in NPS R-467 group and NPS S-467 15 minutes after the reagents were added (1.8 ng/10(5) cells). In the NPS S-467 group, the PTH secretion was elevated along with the culture time, at 60 minutes up to 2.3 ng/10(5) cells. The PTH concentration of NPS R-467 was 80% of that of control group 30 minutes later and 60% of that in control group 60 munites later. No difference was found among the effects of NPS R-467 at different concentrations. CONCLUSION: The calcimimetic NPS R-467 significantly suppresses the PTH secretion, even in severe uremic hyperparathyroidisim patient. It is an effective medicine for hyperparathyroidism.