1133 Journal of Toxicology and Environmental Health, Part A, 69:1133–1143, 2006 Copyright© Taylor & Francis Group, LLC ISSN: 1528–7394 print / 1087–2620 online DOI: 10.1080/15287390500362394 MERCURY BUT NOT ORGANOCHLORINES INHIBITS MUSCARINIC CHOLINERGIC RECEPTOR BINDING IN THE CEREBRUM OF RINGED SEALS (PHOCA HISPIDA) Niladri Basu 1 , Michael Kwan 2 , Hing Man Chan 3,4 1 Department of Natural Resource Sciences and Center for Indigenous Peoples’ Nutrition and Environment (CINE), McGill University, Ste. Anne de Bellevue, Quebec 2 Makivik Research Centre, Kuujjuaq, Quebec 3 School of Dietetics and Human Nutrition and Center for Indigenous Peoples’ Nutrition and Environment (CINE), McGill University, Ste. Anne de Bellevue, Quebec, Canada 4 Community Health Program, University of Northern British Columbia, Prince George, British Columbia, Canada 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 (Hg 2+ ), p,p¢-DDT, Arochlor 1254, chlordane, dieldrin, lindane, and toxaphene on [ 3 H]quinuclidinyl benzilate ([ 3 H]-QNB) binding to the muscarinic cholinergic (mACh) receptor in cellular membranes isolated from the cerebrum of ringed seals (Phoca hispida). [ 3 H]-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 Hg 2+ were the only neurotoxicants that inhibited radioligand binding by greater than 50%. Hg 2+ was significantly more potent at inhibiting mACh receptor binding than MeHg + when the IC 50 data were compared (IC 50 = 1.92 ± 0.06 mM versus 2.75 ± 0.22 mM), but when the data were normalized to derive inhibition constants (K i ) there was no statis- tical difference in inhibition (Hg 2+ = 1.38 ± 0.07 mM; MeHg + = 1.26 ± 0.12 mM ). Toxaphene also inhibited mACh receptor binding by 22.4%, but this was only significant at the highest concentration tested (320 mM). Overall, these data suggest that Hg, and not organochlorines, inhibits ligand binding to the mACh receptor. These mechanistic findings may be used to sup- port and develop specific biomarkers of Hg exposure and neurotoxicity in sensitive ecological species. Received 15 February 2005; accepted 18 May 2005. This study was funded by Collaborative Mercury Research Network (COMERN) and National Sciences and Engineering Research Council (NSERC) of Canada Discovery Research Grants to H. M. Chan. Samples were collected under the Northern Contaminants Program, Canada. Assistance by Christopher J. Stamler, Sonja Ostertag, and Donna Leggee is greatly appreciated. Address correspondence to Hing Man Chan, Community Health Program, University of Northern British Columbia, 3333 University Way, Prince George, British Columbia, Canada, V2N 4Z9. E-mail: LChan@unbc.ca