ArticleJournal of cell science2011
Identifying an uptake mechanism for the antiepileptic and bipolar disorder treatment valproic acid using the simple biomedical model Dictyostelium.
Article in Journal of cell science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Continuous-Flow Synthesis of Antiepileptic Drugs: Process Intensification, Sustainability Metrics, and Scalable Manufacturing.ACS omega · 2026Review
- Characterizing the Role ofBiology · 2025Article
- Formulation and Evaluation of Valproic Acid Microemulsions for Enhanced Transfollicular Delivery in Guinea Pig Skin.Journal of cosmetic dermatology · 2025Article
- Short- and Long-Term Neurobehavioral Effects of Developmental Exposure to Valproic Acid in Zebrafish.International journal of molecular sciences · 2024Article
- Chemotherapy in pediatric brain tumor and the challenge of the blood-brain barrier.Cancer medicine · 2023Review
- Valproic acid affects neurogenesis during early optic tectum development in zebrafish.Biology open · 2023Article
- Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis.Journal of biomedical science · 2022Article
- Insights into Structural Modifications of Valproic Acid and Their Pharmacological Profile.Molecules (Basel, Switzerland) · 2021Review
- Dictyostelium discoideum as a non-mammalian biomedical model.Microbial biotechnology · 2021Review
- Review
- All You Need Is Fats-for Seizure Control: Using Amoeba to Advance Epilepsy Research.Frontiers in cellular neuroscience · 2018Review
- Developmental profiling of ASD-related shank3 transcripts and their differential regulation by valproic acid in zebrafish.Development genes and evolution · 2016Article
- Valproic acid suppresses collagen by selective regulation of Smads in conjunctival fibrosis.Journal of molecular medicine (Berlin, Germany) · 2016Article
- The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease.European journal of pharmacology · 2015Article
- Valproate-induced neurodevelopmental deficits in Xenopus laevis tadpoles.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a TRPP2 (polycystin-2)-dependent manner.British journal of pharmacology · 2014Article
- An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum.Journal of cell science · 2014Article
- A novel human receptor involved in bitter tastant detection identified using Dictyostelium discoideum.Journal of cell science · 2013Article
- The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters.Physiological reviews · 2013Review
- Bestatin inhibits cell growth, cell division, and spore cell differentiation in Dictyostelium discoideum.Eukaryotic cell · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Valproic acid (VPA) is the most highly prescribed epilepsy treatment worldwide and is also used to prevent bipolar disorder and migraine. Surprisingly, very little is known about its mechanisms of cellular uptake. Here, we employ a range of cellular, molecular and genetic approaches to characterize VPA uptake using a simple biomedical model, Dictyostelium discoideum. We show that VPA is taken up against an electrochemical gradient in a dose-dependent manner. Transport is protein-mediated, dependent on pH and the proton gradient and shows strong substrate structure specificity. Using a genetic screen, we identified a protein homologous to a mammalian solute carrier family 4 (SLC4) bicarbonate transporter that we show is involved in VPA uptake. Pharmacological and genetic ablation of this protein reduces the uptake of VPA and partially protects against VPA-dependent developmental effects, and extracellular bicarbonate competes for VPA uptake in Dictyostelium. We further show that this uptake mechanism is likely to be conserved in both zebrafish (Danio rerio) and Xenopus laevis model systems. These results implicate, for the first time, an uptake mechanism for VPA through SLC4-catalysed activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.