PMID- 16728376
OWN - NLM
STAT- MEDLINE
DCOM- 20060622
LR  - 20131121
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 69
IP  - 12
DP  - 2006 Jun
TI  - Mercury but not organochlorines inhibits muscarinic cholinergic receptor binding 
      in the cerebrum of ringed seals (Phoca hispida).
PG  - 1133-43
AB  - Elevated concentrations of organochlorines and mercury (Hg) have been reported in 
      marine mammals on a global scale. While risk assessments are generally based on 
      quantifying body burdens of toxicants, much less is known about associated 
      adverse health effects and their underlying mechanisms. The purpose of this study 
      was to characterize the inhibitory effects of methylmercury (MeHg+), mercuric 
      chloride (Hg2+), p,p'-DDT, Arochlor 1254, chlordane,dieldrin, lindane, and 
      toxaphene on [3H]quinuclidinyl benzilate ([3H]-QNB) binding to the muscarinic 
      cholinergic (mACh) receptor in cellular membranes isolated from the cerebrum of 
      ringed seals (Phoca hispida). [3H]-QNB binding to the mACh receptor was saturable 
      with a mean receptor density (B(max)) of 826.9 +/- 68.4 fmol/mg and ligand 
      affinity (K(d)) of 0.31 +/- 0.04 nM. MeHg+ and Hg2+ were the only neurotoxicants 
      that inhibited radioligand binding by greater than 50%. Hg2+ was significantly 
      more potent at inhibiting mACh receptor binding than MeHg+ when the IC50 data 
      were compared (IC50 = 1.92 +/- 0.06 microM versus 2.75 +/- 0.22 microM), but when 
      the data were normalized to derive inhibition constants (K(i)) there was no 
      statistical difference in inhibition (Hg2+ = 1.38 +/- 0.07 mM; MeHg+ = 1.26 +/- 
      0.12 microM). Toxaphene also inhibited mACh receptor binding by 22.4%, but this 
      was only significant at the highest concentration tested (320 microM). Overall, 
      these data suggest that Hg, and not organochlorines,inhibits ligand binding to 
      the mACh receptor. These mechanistic findings may be used to support and develop 
      specific biomarkers of Hg exposure and neurotoxicity in sensitive ecological 
      species.
FAU - Basu, Niladri
AU  - Basu N
AD  - Department of Natural Resource Sciences and Center for Indigenous Peoples' 
      Nutrition and Environment (CINE), McGill University, Ste. Anne de Bellevue, 
      Quebec.
FAU - Kwan, Michael
AU  - Kwan M
FAU - Chan, Hing Man
AU  - Chan HM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - 0 (Insecticides)
RN  - 0 (Methylmercury Compounds)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Water Pollutants)
RN  - 53GH7MZT1R (Mercuric Chloride)
SB  - IM
MH  - Animals
MH  - Cell Membrane
MH  - Cells, Cultured
MH  - Hydrocarbons, Chlorinated/*toxicity
MH  - Insecticides/toxicity
MH  - Mercuric Chloride/*toxicity
MH  - Methylmercury Compounds/*toxicity
MH  - Phoca/*physiology
MH  - Receptors, Muscarinic/*drug effects/metabolism
MH  - Telencephalon/metabolism
MH  - Water Pollutants/*toxicity
EDAT- 2006/05/27 09:00
MHDA- 2006/06/23 09:00
CRDT- 2006/05/27 09:00
PHST- 2006/05/27 09:00 [pubmed]
PHST- 2006/06/23 09:00 [medline]
PHST- 2006/05/27 09:00 [entrez]
AID - XU850217512M1509 [pii]
AID - 10.1080/15287390500362394 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 2006 Jun;69(12):1133-43. doi: 
      10.1080/15287390500362394.