Mobilization of intracellular calcium in kidney epithelial cells is inhibited by lead.
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 microM 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 microM, 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.
Olivi
Luisa
L
Department of Neurology, Kennedy Krieger Research Institute, School of Public Health and Hygiene, Johns Hopkins University, 707 N. Broadway, Baltimore, MD 21205, USA.
Cascio
Stacy
S
Wang
Susan
S
Bressler
Joseph
J
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007854:Lead / Q000633:toxicity*; D008301:Maleimides / Q000494:pharmacology; D013997:Time Factors
D007211:Indoles; D008301:Maleimides; D007854:Lead; D000244:Adenosine Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; C070515:bisindolylmaleimide I; D001920:Bradykinin; D002118:Calcium