TY - JOUR

T1 - Molecular cloning, expression and characterization of a bovine serotonin transporter

AU - Mortensen, O V

AU - Kristensen, A S

AU - Rudnick, G

AU - Wiborg, O

N1 - Copyright 1999 Elsevier Science B.V.

PY - 1999/7/23

Y1 - 1999/7/23

N2 - The serotonin transporter (SERT) is a member of a highly homologous family of sodium/chloride dependent neurotransmitter transporters responsible for reuptake of biogenic amines from the extracellular fluid. SERT constitutes the pharmacological target of several clinically important antidepressants. Here we report the molecular cloning of SERT from the bovine species. Translation of the nucleotide sequence revealed 44 amino acid differences compared to human SERT. When transiently expressed in HeLa cells and compared with rat and human SERTs the K(m) value for uptake was increased 2-fold. V(max) and B(max) were both increased about 4-fold indicating the turnover number is conserved. The pharmacological profile revealed a decreased sensitivity towards imipramine, desipramine, citalopram, fluoxetine and paroxetine compared with human SERT, while the sensitivity towards 3, 4-methylenedioxymethamphetamine (MDMA) was mainly unchanged. RT-PCR amplification of RNA from different tissues demonstrated expression of SERT in placenta, brain stem, bone marrow, kidney, lung, heart, adrenal gland, liver, parathyroid gland, thyroid gland, small intestine and pancreas.

AB - The serotonin transporter (SERT) is a member of a highly homologous family of sodium/chloride dependent neurotransmitter transporters responsible for reuptake of biogenic amines from the extracellular fluid. SERT constitutes the pharmacological target of several clinically important antidepressants. Here we report the molecular cloning of SERT from the bovine species. Translation of the nucleotide sequence revealed 44 amino acid differences compared to human SERT. When transiently expressed in HeLa cells and compared with rat and human SERTs the K(m) value for uptake was increased 2-fold. V(max) and B(max) were both increased about 4-fold indicating the turnover number is conserved. The pharmacological profile revealed a decreased sensitivity towards imipramine, desipramine, citalopram, fluoxetine and paroxetine compared with human SERT, while the sensitivity towards 3, 4-methylenedioxymethamphetamine (MDMA) was mainly unchanged. RT-PCR amplification of RNA from different tissues demonstrated expression of SERT in placenta, brain stem, bone marrow, kidney, lung, heart, adrenal gland, liver, parathyroid gland, thyroid gland, small intestine and pancreas.

KW - Amino Acid Sequence

KW - Animals

KW - Carrier Proteins

KW - Cattle

KW - Citalopram

KW - Cloning, Molecular

KW - Desipramine

KW - Female

KW - Fluoxetine

KW - HeLa Cells

KW - Humans

KW - Imipramine

KW - Kinetics

KW - Membrane Glycoproteins

KW - Membrane Transport Proteins

KW - Molecular Sequence Data

KW - N-Methyl-3,4-methylenedioxyamphetamine

KW - Nerve Tissue Proteins

KW - Organ Specificity

KW - Paroxetine

KW - Phylogeny

KW - Pregnancy

KW - Rats

KW - Recombinant Proteins

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sequence Alignment

KW - Sequence Homology, Amino Acid

KW - Serotonin

KW - Serotonin Plasma Membrane Transport Proteins

KW - Transfection

M3 - Journal article

C2 - 10407194

VL - 71

SP - 120

EP - 126

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -