Schricker K, Della Bruna R, Kurtz A
Institut für Physiologie, Universität Regensburg, Germany.
Pflugers Arch. 1993 Apr;423(1-2):14-20. doi: 10.1007/BF00374955.
Utilizing primary cultures of mouse renal juxtaglomerular cells we found that renin secretion during 20 h of incubation was stimulated by 100% when extracellular calcium was lowered from a basal level of 0.5 mM to below 1 microM, and was enhanced in a concentration-dependent fashion by 600% when extracellular calcium was increased up to 10 mM. The stimulatory effect of low calcium on renin secretion was apparent after the first hour of incubation, whereas the stimulatory effect of increased calcium occurred with a delay of at least 1 h. During the first hour of incubation increased extracellular calcium blunted the stimulation of renin secretion induced by forskolin (10 microM). The stimulatory effect of increased calcium was attenuated in the presence of 8-pCPT-cGMP, a membrane-permeable cGMP analogue, and in the presence of 100 mM sucrose. The stimulatory effect of increased calcium was blunted in the presence of 0.5 mM cobalt, which itself stimulated renin secretion at normal (0.5 mM) calcium concentrations. Renin synthesis by the cultured cells at low calcium was markedly attenuated in proportion with total protein synthesis, whereas renin synthesis was not altered at increased calcium concentrations. Our findings suggest that a rise of intracellular calcium, induced by an increase of extracellular calcium, is associated with a transient inhibition followed by a marked and regulatable stimulation of renin secretion. Neither calcium depletion nor calcium elevation appears to exert specific effects on renin synthesis in juxtaglomerular cells.
利用小鼠肾近球细胞的原代培养物,我们发现,在孵育20小时期间,当细胞外钙从基础水平0.5 mM降至1 μM以下时,肾素分泌增加了100%,而当细胞外钙增加至10 mM时,肾素分泌以浓度依赖的方式增加了600%。低钙对肾素分泌的刺激作用在孵育的第一小时后就很明显,而钙增加的刺激作用则至少延迟1小时才出现。在孵育的第一小时内,细胞外钙增加减弱了福斯高林(10 μM)诱导的肾素分泌刺激。在存在膜通透性cGMP类似物8-pCPT-cGMP和100 mM蔗糖的情况下,钙增加的刺激作用减弱。在存在0.5 mM钴的情况下,钙增加的刺激作用减弱,而钴本身在正常(0.5 mM)钙浓度下会刺激肾素分泌。低钙条件下培养细胞的肾素合成与总蛋白合成成比例地显著减弱,而在钙浓度增加时肾素合成没有改变。我们的研究结果表明,细胞外钙增加诱导的细胞内钙升高与肾素分泌的短暂抑制相关,随后是显著且可调节的刺激。钙耗竭和钙升高似乎都不会对近球细胞中的肾素合成产生特异性影响。