Inhibition of antagonist binding to human brain muscarinic receptor by vanadium compounds.
Metavanadate, orthovanadate, and pervanadate all inhibited [3H]QNB antagonist binding to the human brain muscarinic acetylcholine receptor (mAChR) in the presence of glutathione, with the order of decreasing potency and the concentration required for 50% inhibition (I[50]) being: pervanadate (95 microM) > orthovanadate (132 microM) > metavanadate (452 microM). Omission of glutathione decreased the inhibition of the vanadium compounds 2-6-fold. Preincubating the vanadium compounds with the mAChR in the presence of glutathione at 37 degrees for 1 h markedly decreased the I(50) values as follows: pervanadate (13 microM) > orthovanadate (46 microM) > metavanadate (118 microM). Inhibition by the vanadium compounds was blocked by EDTA, Mn2+, and Trolox, a water-soluble vitamin E analog. Vanadium use in treating diabetes is discussed regarding its inhibition of mAChR function.
Venters
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Department of Neurology, The Alzheimer's Treatment and Research Center, St. Paul Ramsey Medical Center, MN 55101-2595, USA.
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D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009044:Motor Cortex / Q000187:drug effects* / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C076715:pervanadate; D014638:Vanadates; D011813:Quinuclidinyl Benzilate; D005978:Glutathione