Mobilization of intracellular calcium in kidney epithelial cells is inhibited by lead

Luisa Olivi, Stacy Cascio, Susan Wang, Joseph Bressler

Research output: Contribution to journalArticle

Abstract

The effect of lead (Pb) on intracellular calcium (Cai) after stimulation with agonists was studied in Madin-Darby canine kidney (MDCK) cells. In response to the agonist ADP, the levels of Cai increased by approximately threefold in MDCK cells bathed in a buffer with calcium (Ca) or in a buffer with nominal Ca. Pb inhibited the response to ADP in MDCK cells bathed in either buffer. The inhibition by Pb was observed after a 5 and 20-min exposure to Pb, but not after 2-min. Very high concentrations of ADP did not reverse the effects of Pb. Concentrations of Pb of 1 μM or more inhibited the response to ADP. Similarly, the response to bradykinin was also inhibited by Pb. Protein kinase C did not play a role since the protein kinase C inhibitor GF 109203X did not reverse the effects of Pb. Interestingly, MDCK cells treated with Pb at concentrations above 1 μM, for periods of 5-20 min, displayed elevated levels of inositol 1,4,5-trisphosphate. In conclusion, Pb inhibits mobilization of Cai after agonist stimulation by a mechanism that is unrelated to the type of agonist used. Evidence is presented suggesting that the inhibition is due to increases in levels of inositol 1,4,5-trisphosphate, which possibly decreases the amount of Cai available for mobilization.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalToxicology
Volume176
Issue number1-2
DOIs
StatePublished - Jul 1 2002

Keywords

  • Bradykinin
  • Intracellular calcium
  • Madin-Darby canine kidney cells
  • Pb inhibition

ASJC Scopus subject areas

  • Toxicology

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