CALMODULIN ANTAGONISTS STIMULATE RENIN SECRETION AND INHIBIT RENIN SYNTHESIS INVITRO
CALMODULIN ANTAGONISTS STIMULATE RENIN SECRETION AND INHIBIT RENIN SYNTHESIS INVITRO
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DOI：
10.1152/ajprenal.1992.262.3.f397
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发表时间：
1992-03-01
影响因子：
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通讯作者：
KURTZ, A
中科院分区：
文献类型：
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作者：
DELLABRUNA, R;PINET, F;KURTZ, A
为了查明钙调蛋白活性是否可能是肾素分泌和合成的细胞控制的共同点，我们研究了钙调蛋白拮抗剂对小鼠肾小球旁（JG）细胞原代培养物中肾素分泌和合成的影响。我们发现钙调素拮抗剂卡咪唑铵 (CMDZ)、N-(6-氨基己基)-5-氯-1-萘磺酰胺 (W-7) 和三氟拉嗪 (TFP) 强烈刺激分离的 JG 细胞释放肾素，效力顺序为 CMDZ > TFP > W-7。 CMDZ、TFP 和 W-7 也抑制肾素的从头合成，与肾素分泌的效力顺序相同。肾素合成的减少与培养的 JG 细胞中蛋白质合成的普遍抑制同时发生。使用放线菌酮实现了与 CMDZ 相当的对总蛋白合成和肾素合成的抑制。然而，放线菌酮在孵育 20 小时内并没有改变肾素分泌。综上所述，我们的研究结果表明，钙调蛋白活性的抑制对肾 JG 细胞中肾素的胞吐作用具有强大的刺激作用。另一方面，钙调蛋白活性也是 JG 细胞中蛋白质和肾素合成所必需的。因此，钙调蛋白活性不太可能与 JG 细胞中的肾素合成和肾素分泌呈正相关。
To find out whether calmodulin activity could be a common denominator for the cellular control of renin secretion and synthesis, we have examined the effects of calmodulin antagonists on the secretion and the synthesis of renin in primary cultures of mouse juxtaglomerular (JG) cells. We found that the calmodulin antagonists calmidazolium (CMDZ), N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), and trifluoperazine (TFP) strongly stimulated renin release from isolated JG cells with a rank order of potency CMDZ > TFP > W-7. With the same order of potency as on renin secretion, CMDZ, TFP, and W-7 also inhibited de novo synthesis of renin. This decrease of renin synthesis went in parallel with a general inhibition of protein synthesis in the cultured JG cells. A comparable inhibition of total protein synthesis and renin synthesis as with CMDZ was achieved with cycloheximide. Cycloheximide, however, did not alter renin secretion within 20 h of incubation. Taken together, our findings suggest that inhibition of calmodulin activity exerts a powerful stimulatory effect on the exocytosis of renin in renal JG cells. Calmodulin activity on the other hand is also essentially required for protein and renin synthesis in JG cells. It is not very likely therefore that calmodulin activity positively links renin synthesis and renin secretion in JG cells.