Molecular and functional characterization of the Gulf toadfish serotonin transporter SLC6A4

• Published in: Journal of experimental biology Vol. 221; no. Pt 7; p. jeb170928
• Main Authors: Amador, Molly H B, McDonald, M Danielle
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.04.2018
• Subjects: Amino Acid Sequence; Amino acids; Animals; Batrachoididae; Batrachoidiformes - genetics; Batrachoidiformes - metabolism; Brain; Cerebellum; Danio rerio; Fish Proteins - chemistry; Fish Proteins - genetics; Fish Proteins - metabolism; Fluoxetine; Fluoxetine - pharmacology; Gene Expression Profiling; Heart; Inhibition; Kinetics; mRNA; Oocytes; Phylogeny; Platelets; Sequence Alignment - veterinary; Serotonin; Serotonin - pharmacology; Serotonin Plasma Membrane Transport Proteins - chemistry; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin transporter; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - pharmacology; Tissues; Zebrafish; 5-HTT; 5-Hydroxytryptamine; 5-HT; Opsanus beta; Transport kinetics; mRNA expression
• ISSN: 0022-0949; 1477-9145
• DOI: 10.1242/jeb.170928

The serotonin transporter (SERT) functions in the uptake of the neurotransmitter serotonin (5-HT) from the extracellular milieu and is the molecular target of the selective serotonin re-uptake inhibitors (SSRIs), a common group of anti-depressants. The current study comprehensively assesses the sequence, tissue distribution, transport kinetics and physiological function of a teleost SERT. The 2022 bp toadfish SERT sequence encodes a protein of 673 amino acids, which shows 83% similarity to zebrafish SERT and groups with SERT of other teleosts in phylogenetic analysis. SERT mRNA is ubiquitous in tissues and is expressed at high levels in the heart and, within the brain, in the cerebellum. SERT cRNA expressed in oocytes demonstrates a value of 2.08±0.45 μmol l , similar to previously reported values for zebrafish and human SERT. Acute systemic blockade of SERT by intraperitoneal administration of the SSRI fluoxetine (FLX) produces a dose-dependent increase in plasma 5-HT, indicating effective inhibition of 5-HT uptake from the circulation. As teleosts lack platelets, which are important 5-HT sequestration sites in mammals, the FLX-induced increase in plasma 5-HT suggests that toadfish tissues may normally be responsible for maintaining low 5-HT concentrations in the bloodstream.