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Calmodulin antagonists stimulate renin secretion and inhibit renin synthesis in vitro
R Della Bruna1, F Pinet, P Corvol
1Physiologisches Institut Universität Zurich, Switzerland.
Abstract:
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 greater than TFP greater than 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.
Insights
Calmodulin antagonists stimulate renin secretion from kidney cells but inhibit its synthesis. This suggests calmodulin activity is crucial for renin synthesis but not secretion.
Area of Science:
- Cellular Biology
- Renal Physiology
- Molecular Endocrinology
Background:
- Calmodulin is a key calcium-binding protein involved in cellular signaling.
- The role of calmodulin in the regulation of renin secretion and synthesis is not fully understood.
Purpose of the Study:
- To investigate the role of calmodulin activity in the cellular control of renin secretion and synthesis.
- To determine if calmodulin acts as a common denominator for regulating both processes.
Main Methods:
- Primary cultures of mouse juxtaglomerular (JG) cells were used.
- The effects of various calmodulin antagonists (calmidazolium, W-7, trifluoperazine) on renin secretion and synthesis were examined.
- Cycloheximide was used to assess the impact on protein synthesis.
Main Results:
- Calmodulin antagonists significantly stimulated renin release from JG cells.
- These antagonists also inhibited de novo renin synthesis in a manner parallel to general protein synthesis inhibition.
- Cycloheximide inhibited both total and renin synthesis but did not affect renin secretion.
Conclusions:
- Inhibition of calmodulin activity strongly stimulates renin exocytosis in renal JG cells.
- Calmodulin activity is essential for both protein and renin synthesis.
- Calmodulin activity does not appear to positively link renin synthesis and secretion in JG cells.