{"doi":"10.1016/j.neuint.2007.06.022","title":"Genetic deletion of vesicular monoamine transporter-2 (VMAT2) reduces dopamine transporter activity in mesencephalic neurons in primary culture","abstract":null,"journal":"Neurochemistry International","year":2007,"id":596291,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1527125,"name":"Etsuko Kamegaya","orcid":null,"position":1,"is_corresponding":false},{"id":1144968,"name":"Yoko Hagino","orcid":null,"position":2,"is_corresponding":false},{"id":1527126,"name":"Kazuhide Imai","orcid":null,"position":3,"is_corresponding":false},{"id":1527127,"name":"Akihiro Fujikawa","orcid":null,"position":4,"is_corresponding":false},{"id":1527129,"name":"Kohei Tamura","orcid":null,"position":5,"is_corresponding":false},{"id":1527131,"name":"Tomoyuki Enokiya","orcid":null,"position":6,"is_corresponding":false},{"id":1527132,"name":"Toshifumi Yamamoto","orcid":null,"position":7,"is_corresponding":false},{"id":1202645,"name":"Takao Takeshima","orcid":"0000-0003-2678-6956","position":8,"is_corresponding":false},{"id":1527133,"name":"Hisashi Koga","orcid":null,"position":9,"is_corresponding":false},{"id":924988,"name":"George R. Uhl","orcid":"0000-0002-5632-2426","position":10,"is_corresponding":false},{"id":112026,"name":"Kazutaka Ikeda","orcid":"0000-0001-9247-4593","position":11,"is_corresponding":false},{"id":1144507,"name":"Ichiro Sora","orcid":"0000-0003-0741-8373","position":12,"is_corresponding":false},{"id":1527124,"name":"Hideko Yamamoto","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Genetic deletion of vesicular monoamine transporter-2 (VMAT2) reduces dopamine transporter activity in mesencephalic neurons in primary culture","abstract":"Our aim was to investigate whether a defect in vesicular monoamine transporter-2 (VMAT2) activities would affect dopaminergic cell functions or not. We examined mesencephalon dopaminergic cultures prepared from VMAT2 wild-type, heterozygous or homozygous knockout (KO) 14-day-old mouse fetuses to determine the number of tyrosine hydroxylase (TH)-positive cells and dopamine transporter activity. The number of TH-positive cells remained unchanged in the VMAT2-KO cultures. Of interest, the dopamine transporter activity in the homozygous cells was significantly decreased, but not in the heterozygous cells, suggesting that complete deletion of VMAT2 inhibited dopamine transporter function. Furthermore, dopamine transporter activity was prominently decreased in the synaptosomal fraction of neonatal homozygous VMAT2-KO mice compared with that of wild-type/heterozygous VMAT2-KO ones, indicating that VMAT2 activity might be one of the factors regulating dopamine transporter activities. To test this possibility, we used reserpine, a VMAT2 inhibitor. Reserpine (1muM) decreased dopamine transporter activity (approx. 50%) in wild-type and heterozygous VMAT2-KO cultures but not in homozygous ones, indicating that blockade of VMAT2 activity reduced dopamine transporter activity. To investigate possible mechanisms underlying the decreased dopamine transporter activity in VMAT2-KO mice, we measured dopamine transporter activities after 24-48h exposure of primary cultures of mesencephalic neurons to dopamine receptor antagonists, PKC inhibitor, PI(3)K inhibitor, and l-DOPA. Among these drugs, l-DOPA slightly reduced the dopamine transporter activities of all genotypes, but the other drugs could not. Since the ratios of reduction in dopamine transporter activity of each genotype treated with l-DOPA were similar, substrate inhibition of dopamine transporters was not the main mechanism underlying the reduced dopamine transporter activity due to genetic deletion of VMAT2. Our results demonstrate that genetic deletion of VMAT2 did not induce immediate cell death but did markedly inhibit dopamine transporter activity.","is_dataset_classified":null,"base_score":3.044522437723423,"endowment":3.044522437723423,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17664021","pmcid":null,"openalex_id":"https://openalex.org/W2060482677","authors":[],"funders":[],"total_grants":0,"fwci":0.6947,"citation_percentile":0.63523233,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2014,"count":5},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":1}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0197018607001647?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0197018607001647?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.neuint.2007.06.022","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17664021","host_type":"repository"}],"fields_of_study":["Neurotransmitter Receptor Influence on Behavior","Neuroscience and Neuropharmacology Research","Pancreatic function and diabetes","Animals","Cell Death","Cells, Cultured","Dopamine","Dopamine Agonists","Dopamine Antagonists","Dopamine Plasma Membrane Transport Proteins","Down-Regulation","Enzyme Inhibitors","Female","Gene Expression Profiling","Gene Expression Regulation","Male","Mesencephalon","Mice","Mice, Knockout","Neurons","Presynaptic Terminals","Synaptic Transmission","Tyrosine 3-Monooxygenase","Vesicular Monoamine Transport Proteins"],"mesh_terms":["Animals","Cells, Cultured","Dopamine","Enzyme Inhibitors","Female","Gene Expression Regulation","Male","Mesencephalon","Synaptic Transmission","Neurons","Tyrosine 3-Monooxygenase","Down-Regulation","Cell Death","Presynaptic Terminals","Mice, Knockout","Dopamine Agonists","Dopamine Antagonists","Gene Expression Profiling","Dopamine Plasma Membrane Transport Proteins","Vesicular Monoamine Transport Proteins","Mice"],"keywords":["Dopamine transporter","Dopamine","Vesicular monoamine transporter","Dopaminergic","Vesicular monoamine transporter 2","Reserpine","Endocrinology","Dopamine Plasma Membrane Transport Proteins","Internal medicine","Biology","Tyrosine hydroxylase","Monoamine neurotransmitter","Chemistry","Pharmacology","Serotonin","Biochemistry","Receptor","Medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T09:42:04.725415Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}