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The in vivo and in vitro effect of calmodulin antagonists on the renal actions of 25(OH) vitamin D3 in the rat

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Abstract

Previous work from this laboratory has demonstrated that 25(OH) vitamin D3 [25(OH)D3] acutely suppresses the phosphaturic action of parathyroid hormone (PTH) and interferes with the PTH-induced activation of adenylate cyclase (AC). Calmodulin inhibitors block vitamin D-induced Ca2+ transport in the gut and phosphorus uptake in renal BBMV's. We have examined whether calmodulin antagonists affect the renal action of 25(OH)D3. Acute clearance experiments were performed in PTH-infused parathyroidectomized rats receiving 25(OH)D3 after pretreatment with trifluoperazine (TFP) or promethazine (P). In vitro PTH-induced activation of renal AC was also studied in membrane preparations from pretreated rats in the presence of 25(OH)D3. 25(OH)D3 reduced the PTH-stimulated increase in fractional excretion of phosphorus (CP/CIn) from 0.292±0.024 to 0.195±0.018 (p<0.005) and urinary cAMP from 149.3±20.3 to 78.1±10.4 pmol/min (p<0.01) and also blunted AC activation in vitro. TFP but not P abolished the effects of 25(OH)D3 both in vivo and in vitro. R 24571 also abolished the in vitro effect of 25(OH)D3. Thus, (1) TFP abolishes both the antiphosphaturic and the AC/cAMP-related actions of 25(OH)D3, (2) P does not have these effects, and (3) R 24571 abolishes the in vitro effect of 25(OH)D3. These results suggest that the antiphosphaturic effect of 25(OH)D3 acting via the AC/cAMP system may be calmodulin dependent.

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Authors and Affiliations

  1. Nephrology Services, Hadassah University Hospital, P. O. Box 1200, 91120, Jerusalem, Israel

    Michael M. Friedlaender, David Darmon, Hanna Wald & Mordecai M. Popovtzer

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  1. Michael M. Friedlaender
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  2. David Darmon
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  3. Hanna Wald
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  4. Mordecai M. Popovtzer
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Friedlaender, M.M., Darmon, D., Wald, H. et al. The in vivo and in vitro effect of calmodulin antagonists on the renal actions of 25(OH) vitamin D3 in the rat. Pflügers Arch 415, 372–380 (1989). https://doi.org/10.1007/BF00370890

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  • DOI: https://doi.org/10.1007/BF00370890

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