[(3)H] 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 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 [(3)H] citalopram indicated that golden shiner SERT has a K(D) of 7 +/- 3 nM and a B(max) of 226 +/- 46 fmol/mg protein. These values are similar to those of rat cortical SERT (K(D) 1.4 +/- 0.1 nM and B(max) 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 [(3)H] nisoxetine, had K(D) = 12 +/- 5 nM and B(max) = 187 +/- 49 fmol/mg protein, whereas rat hippocampal NET had K(D) = 5 +/- 2 nM and B(max) = 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 < 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.
Gould
Georgianna G
GG
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. gouldg@uthscsa.edu
Brooks
Bryan W
BW
Frazer
Alan
A
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004390:Chlorpyrifos / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology*; D003530:Cyprinidae / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology
D004390:Chlorpyrifos; D002800:Cholinesterase Inhibitors; D015283:Citalopram; D003891:Desipramine; D018765:Dopamine Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C043425:vanoxerine