title: The effects of mercury on muscarinic cholinergic receptor subtypes (M1 and M2) in captive mink.
abstract: 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.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA. niladri@umich.edu
authors.forename: Niladri
authors.initials: N
authors.lastname: Basu
authors.forename: Anton M
authors.initials: AM
authors.lastname: Scheuhammer
authors.forename: Kirsti
authors.initials: K
authors.lastname: Rouvinen-Watt
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Evans
authors.forename: Nicole
authors.initials: N
authors.lastname: Grochowina
authors.forename: Laurie H M
authors.initials: LH
authors.lastname: Chan
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005506:Food Contamination; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D008907:Mink; D018727:Muscarinic Antagonists / Q000378:metabolism; D009778:Occipital Lobe / Q000187:drug effects* / Q000378:metabolism; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism; D011869:Radioligand Assay; D043643:Receptor, Muscarinic M1 / Q000187:drug effects* / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
chemical_list: D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D014316:Tritium; C065959:AFDX 384; D010890:Pirenzepine; C004925:methylmercuric chloride