title: Mercury but not organochlorines inhibits muscarinic cholinergic receptor binding in the cerebrum of ringed seals (Phoca hispida).
abstract: 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.
authors.affiliation: Department of Natural Resource Sciences and Center for Indigenous Peoples' Nutrition and Environment (CINE), McGill University, Ste. Anne de Bellevue, Quebec.
authors.forename: Niladri
authors.initials: N
authors.lastname: Basu
authors.forename: Michael
authors.initials: M
authors.lastname: Kwan
authors.forename: Hing Man
authors.initials: HM
authors.lastname: Chan
mesh_terms: D000818:Animals; D002462:Cell Membrane; D002478:Cells, Cultured; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity; D008627:Mercuric Chloride / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D046049:Phoca / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism; D014873:Water Pollutants / Q000633:toxicity*
chemical_list: D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D008767:Methylmercury Compounds; D011976:Receptors, Muscarinic; D014873:Water Pollutants; D008627:Mercuric Chloride