PMID- 10869474
OWN - NLM
STAT- MEDLINE
DCOM- 20000818
LR  - 20191210
IS  - 0003-9969 (Print)
IS  - 0003-9969 (Linking)
VI  - 45
IP  - 8
DP  - 2000 Aug
TI  - Effects of low concentrations of paraoxon on Ca(2+) mobilization in a human 
      parotid salivary cell-line HSY.
PG  - 621-38
AB  - 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 (IP(3)) formation and Ca(2+) 
      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 Ca(2+) ([Ca(2+)](i)). This increase was 
      abolished by atropine. Ca(2+) release from the IP(3)-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, IP(3) formation was inhibited by 
      paraoxon but mChR expression was not altered. Although IP(3) receptor expression 
      was not changed, Ca(2+) release elicited by IP(3) 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 IP(3) receptors. 
      Paraoxon exposure also induced a concentration-dependent reduction in the total 
      capacity of intracellular Ca(2+) stores, whereas the capacity of the 
      IP(3)-sensitive Ca(2+) store was not altered by paraoxon, as judged by 
      discharging of the IP(3)-sensitive Ca(2+) store with thapsigargin (TG). Ca(2+) 
      influx stimulated by ACh or ATP was also enhanced by 0.1 nM, but not 1 and 10 nM, 
      paraoxon. On the other hand, Ca(2+) influx activated by TG was enhanced by 
      exposure to all concentrations of paraoxon, indicating that paraoxon modulates 
      the Ca(2+) entry pathway. These results suggest that low concentrations of 
      paraoxon interact with elements of the PI pathway, enhancing Ca(2+) release and 
      influx mechanisms.
FAU - Sun, X
AU  - Sun X
AD  - Department of Pediatrics, University of Texas Health Science Center, 7703 Floyd 
      Curl Drive, San Antonio, TX 78284, USA.
FAU - Liu, X B
AU  - Liu XB
FAU - Martinez, J R
AU  - Martinez JR
FAU - Zhang, G H
AU  - Zhang GH
LA  - eng
GR  - DE09270/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Arch Oral Biol
JT  - Archives of oral biology
JID - 0116711
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insecticides)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Purinergic P2 Receptor Agonists)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Streptolysins)
RN  - 0 (streptolysin O)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7C0697DR9I (Atropine)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - N9YNS0M02X (Acetylcholine)
RN  - Q9CX8P80JW (Paraoxon)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Adenosine Triphosphate/pharmacology
MH  - Analysis of Variance
MH  - Atropine/pharmacology
MH  - Bacterial Proteins
MH  - Calcium Signaling/*drug effects
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Cell Line
MH  - Cholinesterase Inhibitors/administration & dosage/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Inositol 1,4,5-Trisphosphate/antagonists & inhibitors/biosynthesis
MH  - Insecticides/administration & dosage/*pharmacology
MH  - Muscarinic Antagonists/pharmacology
MH  - Paraoxon/administration & dosage/*pharmacology
MH  - Parotid Gland/cytology/*drug effects
MH  - Phosphatidylinositols/metabolism
MH  - Purinergic P2 Receptor Agonists
MH  - Receptors, Muscarinic/drug effects
MH  - Signal Transduction/drug effects
MH  - Streptolysins/pharmacology
MH  - Thapsigargin/pharmacology
EDAT- 2000/06/28 11:00
MHDA- 2000/08/29 11:01
CRDT- 2000/06/28 11:00
PHST- 2000/06/28 11:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/06/28 11:00 [entrez]
AID - S0003-9969(00)00043-1 [pii]
AID - 10.1016/s0003-9969(00)00043-1 [doi]
PST - ppublish
SO  - Arch Oral Biol. 2000 Aug;45(8):621-38. doi: 10.1016/s0003-9969(00)00043-1.