TY - JOUR
T1 - Mobilization of intracellular calcium in kidney epithelial cells is inhibited by lead
AU - Olivi, Luisa
AU - Cascio, Stacy
AU - Wang, Susan
AU - Bressler, Joseph
N1 - Funding Information:
The authors would like to thank Dr Pamela Talalay and Ms Angela T. Williams for their assistance in the preparation of this article. Contract grant sponsor: NIH; Contract grant number: RO1 ES08785, Contract grant sponsor: NIEHS; Contract grant number: 03819.
PY - 2002/7/1
Y1 - 2002/7/1
N2 - 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.
AB - 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.
KW - Bradykinin
KW - Intracellular calcium
KW - Madin-Darby canine kidney cells
KW - Pb inhibition
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U2 - 10.1016/S0300-483X(02)00092-6
DO - 10.1016/S0300-483X(02)00092-6
M3 - Article
C2 - 12062925
AN - SCOPUS:0036644148
SN - 0300-483X
VL - 176
SP - 1
EP - 9
JO - Toxicology
JF - Toxicology
IS - 1-2
ER -