[3H] Citalopram Binding to Serotonin Transporter Sites in Minnow Brains

:  Mammalian serotonin (SERT) and norepinephrine transporters (NET) are target sites for antidepressants and are affected by pesticide exposures. Herein, we examined whether golden shiner (Notemigonus crysoleucas) or fathead minnow (Pimphales promelas) SERTs and catecholamine transporters respond co...

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Veröffentlicht in:Basic & clinical pharmacology & toxicology 2007-09, Vol.101 (3), p.203-210
Hauptverfasser: Gould, Georgianna G., Brooks, Bryan W., Frazer, Alan
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container_title Basic & clinical pharmacology & toxicology
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creator Gould, Georgianna G.
Brooks, Bryan W.
Frazer, Alan
description :  Mammalian serotonin (SERT) and norepinephrine transporters (NET) are target sites for antidepressants and are affected by pesticide exposures. Herein, we examined whether golden shiner (Notemigonus crysoleucas) or fathead minnow (Pimphales promelas) SERTs and catecholamine transporters respond comparably to mammalian SERTs and NETs. We compared the pharmacological profiles of central SERT and NET binding sites of the golden shiner minnow to those of rats. Homogenate binding with the radioligand [3H] citalopram indicated that golden shiner SERT has a KD of 7 ± 3 nM and a Bmax of 226 ± 46 fmol/mg protein. These values are similar to those of rat cortical SERT (KD 1.4 ± 0.1 nM and Bmax 240 ± 48 fmol/mg protein). We also examined SERT binding in fathead minnow brain, and found it similar to that of the golden shiner. A putative golden shiner NET, measured using [3H] nisoxetine, had KD = 12 ± 5 nM and Bmax = 187 ± 49 fmol/mg protein, whereas rat hippocampal NET had KD = 5 ± 2 nM and Bmax = 93 ± 8 fmol/mg protein. Minnow SERT and NET binding is displaceable by selective reuptake inhibitors. Finally, we exposed zebrafish (Danio rerio) to the serotonin reuptake inhibiting antidepressant sertraline or the organophosphate chlorpyrifos for 21 days. After either treatment, SERT binding was reduced by 50% (n = 3–6, P 
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Herein, we examined whether golden shiner (Notemigonus crysoleucas) or fathead minnow (Pimphales promelas) SERTs and catecholamine transporters respond comparably to mammalian SERTs and NETs. We compared the pharmacological profiles of central SERT and NET binding sites of the golden shiner minnow to those of rats. Homogenate binding with the radioligand [3H] citalopram indicated that golden shiner SERT has a KD of 7 ± 3 nM and a Bmax of 226 ± 46 fmol/mg protein. These values are similar to those of rat cortical SERT (KD 1.4 ± 0.1 nM and Bmax 240 ± 48 fmol/mg protein). We also examined SERT binding in fathead minnow brain, and found it similar to that of the golden shiner. A putative golden shiner NET, measured using [3H] nisoxetine, had KD = 12 ± 5 nM and Bmax = 187 ± 49 fmol/mg protein, whereas rat hippocampal NET had KD = 5 ± 2 nM and Bmax = 93 ± 8 fmol/mg protein. Minnow SERT and NET binding is displaceable by selective reuptake inhibitors. Finally, we exposed zebrafish (Danio rerio) to the serotonin reuptake inhibiting antidepressant sertraline or the organophosphate chlorpyrifos for 21 days. After either treatment, SERT binding was reduced by 50% (n = 3–6, P &lt; 0.05). In summary, minnow central SERT and NET express slightly lower affinity for antidepressants than rats. 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Herein, we examined whether golden shiner (Notemigonus crysoleucas) or fathead minnow (Pimphales promelas) SERTs and catecholamine transporters respond comparably to mammalian SERTs and NETs. We compared the pharmacological profiles of central SERT and NET binding sites of the golden shiner minnow to those of rats. Homogenate binding with the radioligand [3H] citalopram indicated that golden shiner SERT has a KD of 7 ± 3 nM and a Bmax of 226 ± 46 fmol/mg protein. These values are similar to those of rat cortical SERT (KD 1.4 ± 0.1 nM and Bmax 240 ± 48 fmol/mg protein). We also examined SERT binding in fathead minnow brain, and found it similar to that of the golden shiner. A putative golden shiner NET, measured using [3H] nisoxetine, had KD = 12 ± 5 nM and Bmax = 187 ± 49 fmol/mg protein, whereas rat hippocampal NET had KD = 5 ± 2 nM and Bmax = 93 ± 8 fmol/mg protein. Minnow SERT and NET binding is displaceable by selective reuptake inhibitors. Finally, we exposed zebrafish (Danio rerio) to the serotonin reuptake inhibiting antidepressant sertraline or the organophosphate chlorpyrifos for 21 days. After either treatment, SERT binding was reduced by 50% (n = 3–6, P &lt; 0.05). In summary, minnow central SERT and NET express slightly lower affinity for antidepressants than rats. However, magnitudes of affinity are similar, and minnow SERT binding is decreased by chronic sertraline or chlorpyrifos administration.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Chlorpyrifos - pharmacology</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Citalopram - pharmacology</subject><subject>Cyprinidae - metabolism</subject><subject>Desipramine - pharmacology</subject><subject>Dopamine Uptake Inhibitors - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Norepinephrine Plasma Membrane Transport Proteins - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperazines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Serotonin Plasma Membrane Transport Proteins - metabolism</subject><subject>Serotonin Uptake Inhibitors - pharmacology</subject><subject>Sertraline - pharmacology</subject><issn>1742-7835</issn><issn>1742-7843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtOAyEUhonReKm-gmGju47AMAyzcGEbb0mNJq0rYwjDgKGZQoVpat9eaie6lQ1_ON85nHwAQIwynM7VPMMlJcOS0zwjCJUZQhih7GsPHP8W9n9zXhyBkxjnCJGSYnQIjnDJqhJRcgzu3_KHdzi2nWz9MsgFHFnXWPcBOw-nOvjOO-vgLEgXlz50OsCp7XSE6fHJOufXcBSkdfEUHBjZRn3W3wPwenc7Gz8MJ8_3j-ObyVDlmKBhgUhTUKlYw3jNFce0kbhBKSlmFMY1YSwFYnJTNVI2eVFW2piqrCkxnOp8AC53c5fBf6507MTCRqXbVjrtV1EwjlnBKppAvgNV8DEGbcQy2IUMG4GR2EoUc7H1I7auxFai-JEovlLref_Hql7o5q-xt5aAix6QUcnWJDvKxj-OV5xxyhN3vePWttWbfy8gRuOXWUr5NyXdjNs</recordid><startdate>200709</startdate><enddate>200709</enddate><creator>Gould, Georgianna G.</creator><creator>Brooks, Bryan W.</creator><creator>Frazer, Alan</creator><general>Blackwell Publishing Inc</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200709</creationdate><title>[3H] Citalopram Binding to Serotonin Transporter Sites in Minnow Brains</title><author>Gould, Georgianna G. ; Brooks, Bryan W. ; Frazer, Alan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3120-502d54ac6d68b8c814da1d08c8c6fc11b2666fc2f3f9daad3579eff97b42f84e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Chlorpyrifos - pharmacology</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Citalopram - pharmacology</topic><topic>Cyprinidae - metabolism</topic><topic>Desipramine - pharmacology</topic><topic>Dopamine Uptake Inhibitors - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Norepinephrine Plasma Membrane Transport Proteins - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperazines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Serotonin Plasma Membrane Transport Proteins - metabolism</topic><topic>Serotonin Uptake Inhibitors - pharmacology</topic><topic>Sertraline - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gould, Georgianna G.</creatorcontrib><creatorcontrib>Brooks, Bryan W.</creatorcontrib><creatorcontrib>Frazer, Alan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Basic &amp; clinical pharmacology &amp; toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gould, Georgianna G.</au><au>Brooks, Bryan W.</au><au>Frazer, Alan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>[3H] Citalopram Binding to Serotonin Transporter Sites in Minnow Brains</atitle><jtitle>Basic &amp; clinical pharmacology &amp; toxicology</jtitle><addtitle>Basic Clin Pharmacol Toxicol</addtitle><date>2007-09</date><risdate>2007</risdate><volume>101</volume><issue>3</issue><spage>203</spage><epage>210</epage><pages>203-210</pages><issn>1742-7835</issn><eissn>1742-7843</eissn><abstract>:  Mammalian serotonin (SERT) and norepinephrine transporters (NET) are target sites for antidepressants and are affected by pesticide exposures. Herein, we examined whether golden shiner (Notemigonus crysoleucas) or fathead minnow (Pimphales promelas) SERTs and catecholamine transporters respond comparably to mammalian SERTs and NETs. We compared the pharmacological profiles of central SERT and NET binding sites of the golden shiner minnow to those of rats. Homogenate binding with the radioligand [3H] citalopram indicated that golden shiner SERT has a KD of 7 ± 3 nM and a Bmax of 226 ± 46 fmol/mg protein. These values are similar to those of rat cortical SERT (KD 1.4 ± 0.1 nM and Bmax 240 ± 48 fmol/mg protein). We also examined SERT binding in fathead minnow brain, and found it similar to that of the golden shiner. A putative golden shiner NET, measured using [3H] nisoxetine, had KD = 12 ± 5 nM and Bmax = 187 ± 49 fmol/mg protein, whereas rat hippocampal NET had KD = 5 ± 2 nM and Bmax = 93 ± 8 fmol/mg protein. Minnow SERT and NET binding is displaceable by selective reuptake inhibitors. Finally, we exposed zebrafish (Danio rerio) to the serotonin reuptake inhibiting antidepressant sertraline or the organophosphate chlorpyrifos for 21 days. After either treatment, SERT binding was reduced by 50% (n = 3–6, P &lt; 0.05). In summary, minnow central SERT and NET express slightly lower affinity for antidepressants than rats. However, magnitudes of affinity are similar, and minnow SERT binding is decreased by chronic sertraline or chlorpyrifos administration.</abstract><cop>Malden, USA</cop><pub>Blackwell Publishing Inc</pub><pmid>17697042</pmid><doi>10.1111/j.1742-7843.2007.00100.x</doi><tpages>8</tpages></addata></record>
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subjects Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Chlorpyrifos - pharmacology
Cholinesterase Inhibitors - pharmacology
Citalopram - pharmacology
Cyprinidae - metabolism
Desipramine - pharmacology
Dopamine Uptake Inhibitors - pharmacology
Male
Medical sciences
Norepinephrine Plasma Membrane Transport Proteins - metabolism
Pharmacology. Drug treatments
Piperazines - pharmacology
Rats
Rats, Sprague-Dawley
Serotonin Plasma Membrane Transport Proteins - metabolism
Serotonin Uptake Inhibitors - pharmacology
Sertraline - pharmacology
title [3H] Citalopram Binding to Serotonin Transporter Sites in Minnow Brains
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