Evidence for interference of vitamin D with PTH/PTHrP receptor expression in opossum kidney cells

Hanna Wald*, Michal Dranitzki-Elhalel, R. Backenroth, Mordecai M. Popovtzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Vitamin D counters the phosphaturic action of parathyroid hormone (PTH) in rats in vivo. The present study was undertaken to examine this interaction using monolayers of Opossum kidney (OK) cells. 32P uptake, cAMP generation, PTH/PTHrP receptor mRNA expression and intracellular Ca2+ [Ca2+](i) were measured in (1) control cells, (2) cells exposed to PTH, (3) cells pretreated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and (4) 1,25(OH)2D3- pretreated cells exposed to PTH. 32P uptakes were in (1) 5.00±0.20 (mean ±SE), in (2) 2.30±0.14 (P<0.001 versus group 1), in (3) 4.80±0.24 (P NS versus group 1) and in (4) 3.70±0.20 (P<0.001 versus group 2) nmol P(i)/(mg·prot 10 mm). cAMP levels were in (1) 10±3, in (2) 210±8, in (3) 12±4, and in (4) 122±12 pmol cAMP/mg protein (P<0.001 versus group 2). PTH/PTHrP receptor mRNA expression was in relative units: (1) 100±0, (2) 99.5±6.2, (3) 68.7±2.6 (P<0.001 versus group 1), and (4) 34.8±3.3 (P<0.001 versus group 1). In groups 2 and 4 PTH induced equal transient increments in [Ca2+](i). These experiments demonstrate that the effect of vitamin D on phosphate transport is associated with a commensurate diminution in PTH/PTHrP receptor gene expression and PTH-induced cAMP formation but not with Ca2+ transients. Vitamin D per se does not affect 32P uptake or cAMP generation while it slightly decreased PTH/PTHrP receptor gene expression. These observations demonstrate that: (1) 1.25(OH)2D3 directly antagonizes the effects of PTH on 32P uptake in OK cells, (2) this effect is mediated via inhibition of PTH-induced activation of AC/cAMP system, (3) the diminution in PTH-induced cAMP formation may stem at least in part from a decrease in the expression of PTH/PTHrP receptor mRNA.

Original languageAmerican English
Pages (from-to)289-294
Number of pages6
JournalPflugers Archiv European Journal of Physiology
Volume436
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • 1,25-Dihydroxy-vitamin D
  • Intracellular Ca concentration
  • Opossum kidney cells
  • PTH/PTHrP receptor mRNA
  • Parathyroid hormone cAMP

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