PMID- 18295336 OWN - NLM STAT- MEDLINE DCOM- 20080605 LR - 20131121 IS - 0161-813X (Print) IS - 0161-813X (Linking) VI - 29 IP - 2 DP - 2008 Mar TI - The effects of mercury on muscarinic cholinergic receptor subtypes (M1 and M2) in captive mink. PG - 328-34 LID - 10.1016/j.neuro.2008.01.003 [doi] AB - A combination of in vitro (competitive binding assays) and in vivo (tissues from animals exposed to dietary methyl mercury, MeHg) experimental procedures was employed to assess the effects of mercury (MeHg, HgCl(2)) on the two-key muscarinic cholinergic (mACh) receptor subtypes (M1, M2) in two brain regions (occipital cortex, brain stem) of captive mink (Mustela vison). In vitro, HgCl(2) and MeHg were equipotent in inhibiting [(3)H]-pirenzipine binding to the M1 receptor in the occipital cortex, but in the brain stem, MeHg was about 65x more potent than HgCl(2). For the M2 receptor, both HgCl(2) and MeHg were more potent at inhibiting [(3)H]-AFDX-384 binding in the occipital cortex than in the brain stem. Within each brain region, HgCl(2) was more potent at inhibiting [(3)H]-AFDX-384 binding than MeHg. In vivo exposure of captive mink to MeHg (0.5, 1, and 2ppm MeHg in the diet for 89 days) resulted in greater binding of radioligands to the M1 and M2 receptor in the occipital cortex, but not in the brain stem, when compared to control animals. Based on the in vitro results, we could not conclude which mACh receptor subtype or brain region was most sensitive to Hg, but the in vivo findings suggest that Hg preferentially affects mACh receptor subtype (M1 and M2) levels in the occipital cortex. By studying distinct mACh receptors, these results extend upon previous studies in laboratory rodents and wildlife that showed Hg to affect the global population of mACh receptors. FAU - Basu, Niladri AU - Basu N AD - Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA. niladri@umich.edu FAU - Scheuhammer, Anton M AU - Scheuhammer AM FAU - Rouvinen-Watt, Kirsti AU - Rouvinen-Watt K FAU - Evans, R Douglas AU - Evans RD FAU - Grochowina, Nicole AU - Grochowina N FAU - Chan, Laurie H M AU - Chan LH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080119 PL - Netherlands TA - Neurotoxicology JT - Neurotoxicology JID - 7905589 RN - 0 (Environmental Pollutants) RN - 0 (Methylmercury Compounds) RN - 0 (Muscarinic Antagonists) RN - 0 (Receptor, Muscarinic M1) RN - 0 (Receptor, Muscarinic M2) RN - 10028-17-8 (Tritium) RN - 118290-27-0 (AFDX 384) RN - 3G0285N20N (Pirenzepine) RN - RWZ4L3O1X0 (methylmercuric chloride) SB - IM MH - Animals MH - Binding, Competitive MH - Brain Stem/*drug effects/metabolism MH - Diet MH - Dose-Response Relationship, Drug MH - Environmental Pollutants/*toxicity MH - Food Contamination MH - Male MH - Methylmercury Compounds/*toxicity MH - Mink MH - Muscarinic Antagonists/metabolism MH - Occipital Lobe/*drug effects/metabolism MH - Pirenzepine/analogs & derivatives/metabolism MH - Radioligand Assay MH - Receptor, Muscarinic M1/*drug effects/metabolism MH - Receptor, Muscarinic M2/*drug effects/metabolism MH - Tritium EDAT- 2008/02/26 09:00 MHDA- 2008/06/06 09:00 CRDT- 2008/02/26 09:00 PHST- 2007/10/31 00:00 [received] PHST- 2007/12/06 00:00 [revised] PHST- 2008/01/10 00:00 [accepted] PHST- 2008/02/26 09:00 [pubmed] PHST- 2008/06/06 09:00 [medline] PHST- 2008/02/26 09:00 [entrez] AID - S0161-813X(08)00006-5 [pii] AID - 10.1016/j.neuro.2008.01.003 [doi] PST - ppublish SO - Neurotoxicology. 2008 Mar;29(2):328-34. doi: 10.1016/j.neuro.2008.01.003. Epub 2008 Jan 19.