Title of article :
Effects of low concentrations of paraoxon on Ca2+ mobilization in a human parotid salivary cell-line HSY
Author/Authors :
Sun، نويسنده , , Xiuhua and Liu، نويسنده , , Xiao-Bing and Martinez، نويسنده , , J.Ricardo and Zhang، نويسنده , , Guo H.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2000
Pages :
18
From page :
621
To page :
638
Abstract :
The salivary gland is a target organ of organophosphate pesticides (OPs). Inhibition of acetylcholinesterase (AChE) by OPs leads to a decrease in acetylcholine (ACh) breakdown that results in overstimulation of muscarinic cholinergic receptors (mChR). However, OPs may also directly interact with downstream elements of the phosphoinositide (PI) signalling pathway coupled with mChR. The present study examined the effects of exposure to low concentrations of the OP paraoxon on inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization in response to ACh or ATP in the human parotid cell-line HSY. Exposure to 0.1 and 1 nM, but not 10 nM, paraoxon for 24 hr significantly elevated the basal cytosolic free Ca2+ ([Ca2+]i). This increase was abolished by atropine. Ca2+ release from the IP3-sensitive store in response to ACh or ATP, a P2Y-nucleotide agonist, was significantly increased in cells pre-exposed to 0.1 nM paraoxon. However, IP3 formation was inhibited by paraoxon but mChR expression was not altered. Although IP3 receptor expression was not changed, Ca2+ release elicited by IP3 in streptolysin O toxin-permeabilized cells was significantly larger in cells pre-exposed to 0.1 nM paraoxon, suggesting that paraoxon increases the sensitivity of IP3 receptors. Paraoxon exposure also induced a concentration-dependent reduction in the total capacity of intracellular Ca2+ stores, whereas the capacity of the IP3-sensitive Ca2+ store was not altered by paraoxon, as judged by discharging of the IP3-sensitive Ca2+ store with thapsigargin (TG). Ca2+ influx stimulated by ACh or ATP was also enhanced by 0.1 nM, but not 1 and 10 nM, paraoxon. On the other hand, Ca2+ influx activated by TG was enhanced by exposure to all concentrations of paraoxon, indicating that paraoxon modulates the Ca2+ entry pathway. These results suggest that low concentrations of paraoxon interact with elements of the PI pathway, enhancing Ca2+ release and influx mechanisms.
Keywords :
inositol 1 , 4 , Ca2+ signalling , paraoxon , 5-trisphosphate , ATP , Salivary cells , acetylcholine
Journal title :
Archives of Oral Biology
Serial Year :
2000
Journal title :
Archives of Oral Biology
Record number :
1801662
Link To Document :
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