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Lead inhibits Ca(2+)-stimulated nitric oxide synthase activity from rat cerebellum
Pb2+ is reported to cause cognitive dysfunctions in children and to inhibit long-term potentiation (LTP), a model form of synaptic plasticity that involves nitric oxide (NO). Since Pb2+ interacts with Ca(2+)-calmodulin, and brain nitric oxide synthase (NOS) is Ca(2+)-calmodulin regulated, we examine...
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Published in: | Neuroscience letters 1995-08, Vol.196 (1-2), p.65-68 |
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container_title | Neuroscience letters |
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creator | Quinn, M R Harris, C L |
description | Pb2+ is reported to cause cognitive dysfunctions in children and to inhibit long-term potentiation (LTP), a model form of synaptic plasticity that involves nitric oxide (NO). Since Pb2+ interacts with Ca(2+)-calmodulin, and brain nitric oxide synthase (NOS) is Ca(2+)-calmodulin regulated, we examined the effects of Pb2+ on NOS activity prepared from rat cerebellum. NOS required NADPH and was inhibited by monomethylarginine. Full NOS activity required 0.6 microM free Ca2+ and was inhibited 50% by 17 nM and 100% by 80 nM free Pb2+. NOS inhibition by Pb2+ was reversible by increasing free Ca2+ concentrations. Evaluation of other divalent cations resulted in the following ranked order of potencies: Cu2+ > Pb2+ >> Zn2+; Fe2+, Ba2+, Mg2+, Mn2+, and Sr2+ were ineffective. These results suggest that Pb2+ inhibition of brain NOS activity may account for some of the effects of Pb2+ on the CNS. |
doi_str_mv | 10.1016/0304-3940(95)11845-N |
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Since Pb2+ interacts with Ca(2+)-calmodulin, and brain nitric oxide synthase (NOS) is Ca(2+)-calmodulin regulated, we examined the effects of Pb2+ on NOS activity prepared from rat cerebellum. NOS required NADPH and was inhibited by monomethylarginine. Full NOS activity required 0.6 microM free Ca2+ and was inhibited 50% by 17 nM and 100% by 80 nM free Pb2+. NOS inhibition by Pb2+ was reversible by increasing free Ca2+ concentrations. Evaluation of other divalent cations resulted in the following ranked order of potencies: Cu2+ > Pb2+ >> Zn2+; Fe2+, Ba2+, Mg2+, Mn2+, and Sr2+ were ineffective. These results suggest that Pb2+ inhibition of brain NOS activity may account for some of the effects of Pb2+ on the CNS.</description><identifier>ISSN: 0304-3940</identifier><identifier>DOI: 10.1016/0304-3940(95)11845-N</identifier><identifier>PMID: 7501259</identifier><language>eng</language><publisher>Ireland</publisher><subject>Animals ; Calcium - pharmacology ; Cations - pharmacology ; Cerebellum - drug effects ; Dose-Response Relationship, Drug ; Egtazic Acid - pharmacology ; Lead - pharmacology ; Male ; NADP - pharmacology ; Nitric Oxide Synthase - drug effects ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Neuroscience letters, 1995-08, Vol.196 (1-2), p.65-68</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7501259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quinn, M R</creatorcontrib><creatorcontrib>Harris, C L</creatorcontrib><title>Lead inhibits Ca(2+)-stimulated nitric oxide synthase activity from rat cerebellum</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>Pb2+ is reported to cause cognitive dysfunctions in children and to inhibit long-term potentiation (LTP), a model form of synaptic plasticity that involves nitric oxide (NO). Since Pb2+ interacts with Ca(2+)-calmodulin, and brain nitric oxide synthase (NOS) is Ca(2+)-calmodulin regulated, we examined the effects of Pb2+ on NOS activity prepared from rat cerebellum. NOS required NADPH and was inhibited by monomethylarginine. Full NOS activity required 0.6 microM free Ca2+ and was inhibited 50% by 17 nM and 100% by 80 nM free Pb2+. NOS inhibition by Pb2+ was reversible by increasing free Ca2+ concentrations. Evaluation of other divalent cations resulted in the following ranked order of potencies: Cu2+ > Pb2+ >> Zn2+; Fe2+, Ba2+, Mg2+, Mn2+, and Sr2+ were ineffective. 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subjects | Animals Calcium - pharmacology Cations - pharmacology Cerebellum - drug effects Dose-Response Relationship, Drug Egtazic Acid - pharmacology Lead - pharmacology Male NADP - pharmacology Nitric Oxide Synthase - drug effects Rats Rats, Sprague-Dawley |
title | Lead inhibits Ca(2+)-stimulated nitric oxide synthase activity from rat cerebellum |
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