Linked Life Data

11311448

Source:http://linkedlifedata.com/resource/pubmed/id/11311448

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-4-20
pubmed:abstractText
Astrocytes contain transport systems that are capable of removing various neurotransmitters from the synaptic cleft by transporters present in the plasma membrane. Glial serotonin transporter (SERT) plays an important role in the re-uptake of 5-hydroxytryptamine (5-HT). We examined the pharmacological characterization of 5-HT uptake into rat cortical synaptosomes and cultured rat astrocytes, and the immunodetection of glial SERT proteins using specific site-directed monoclonal antibodies (MoAb). Furthermore, using a reverse transcriptase-polymerase chain reaction (RT-PCR) method, we addressed the expression of SERT mRNA in cultured rat astrocytes. We investigated the inhibitory effects of various monoamine uptake inhibitors on the uptake of [3H]5-HT into cultured astrocytes and cortical synaptosomes. Tricyclic antidepressants (clomipramine and imipramine) as well as selective serotonin re-uptake inhibitors (fluvoxamine, fluoxetine and zimelidine) were very potent inhibitors of [3H]5-HT uptake in both preparations. In contrast, the inhibitory effects of NE uptake inhibitors (nisoxetine and desipramine) and cocaine were weaker than those of 5-HT uptake inhibitors. In addition, dopamine (DA) uptake inhibitors (nomifensine and GBR-12935) exhibited a Ki value in the low micromolar range. The inhibitory potencies were in the order 5-HT uptake inhibitors (clomipramine, fluvoxamine, fluoxetine, imipramine and zimelidine) > NE uptake inhibitors (nisoxetine and desipramine) = cocaine > DA uptake inhibitors (nomifensine and GBR-12935). There was no difference in the order of the inhibitory effects of various monoamine uptake inhibitors between the two preparations. A correlation analysis of the potencies of various monoamine uptake inhibitors in the inhibition of [3H]5-HT into cultured astrocytes and cortical synaptosomes produced a highly significant correlation coefficient of 0.9893 (P < 0.0001). Immunocytochemical staining using anti-SERT MoAb in cultured astrocytes revealed that the plasma membrane, as well as intracellular, perinuclear compartments, presumably endoplasmic reticulum or golgi membranes, showed a considerable level of immunoreactivity. Extracts of astrocytes and synaptosomes from the cortex were immunoblotted with anti-SERT MoAb. SDS-PAGE/Western blots indicate that anti-SERT MoAb recognized two bands of 120 and 73 kDa in both preparations. RT-PCR demonstrated that astrocytes in cultured expressed mRNA for the cloned SERT protein, which has been characterized as the neuronal SERT. These pharmacological experiments indicate that this uptake process takes place through glial SERT that is very similar to neuronal SERT. Furthermore, the present data also indicate that the presence of the mRNA and protein for the neuronal SERT were established in cultured rat astrocytes, and the polypeptide portion of SERT in astrocytes and frontal cortex could be the same gene product.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0197-0186
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39-49
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:11311448-Animals, pubmed-meshheading:11311448-Astrocytes, pubmed-meshheading:11311448-Blotting, Western, pubmed-meshheading:11311448-Carrier Proteins, pubmed-meshheading:11311448-Cells, Cultured, pubmed-meshheading:11311448-Frontal Lobe, pubmed-meshheading:11311448-Immunohistochemistry, pubmed-meshheading:11311448-Membrane Glycoproteins, pubmed-meshheading:11311448-Membrane Transport Proteins, pubmed-meshheading:11311448-Nerve Tissue Proteins, pubmed-meshheading:11311448-Neuroglia, pubmed-meshheading:11311448-RNA, Messenger, pubmed-meshheading:11311448-Rats, pubmed-meshheading:11311448-Rats, Sprague-Dawley, pubmed-meshheading:11311448-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11311448-Serotonin, pubmed-meshheading:11311448-Serotonin Plasma Membrane Transport Proteins
pubmed:year
2001
pubmed:articleTitle
Pharmacological characterization and visualization of the glial serotonin transporter.
pubmed:affiliation
Department of Pharmacology and Intractable Diseases Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, 160-8402, Tokyo, Japan.
pubmed:publicationType
Journal Article