Kinetic Characterization of Inhibition of γ‐Aminobutyric Acid Uptake into Cultured Neurons and Astrocytes by 4,4‐Diphenyl‐3‐Butenyl Derivatives of Nipecotic Acid and Guvacine
- 1 March 1988
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 50 (3) , 818-823
- https://doi.org/10.1111/j.1471-4159.1988.tb02986.x
Abstract
The effects of N-(4,4-diphenyl-3-butenyl) derivatives of nepecotic acid (SKF-89976-A and SKF-100844-A) and guvacine (SKF-100330-A) on neuronal and astroglial .gamma.-aminobutyric acid (GABA) uptake were investigated. In addition, the uptake of SKF-89976-A was studied using the tritiated compound. All of the compounds were found to be competitive inhibitors of GABA uptake irrespective of the cell type, with Ki values similar to or lower than those of the parent amino acids. Moreover, none of the compounds exhibited selectivity with regard to inhibition of neuronal and glial GABA uptake. In spite of the competitive nature of SKF-89976-A, the compound was not transported by the GABA carriers in the two cell types, because no saturable uptake could be demonstrated.Keywords
This publication has 30 references indexed in Scilit:
- Mutual Inhibition Kinetic Analysis of γ‐Aminobutyric Acid, Taurine, and β‐Alanine High‐Affinity Transport into Neurons and Astrocytes: Evidence for Similarity Between the Taurine and β‐Alanine Carriers in Both Cell TypesJournal of Neurochemistry, 1986
- Uptake of GABA and nipecotic acid in astrocytes and neurons in primary cultures: Changes in the sodium coupling ratio during differentiationJournal of Neuroscience Research, 1986
- Amplification by glycine of the anticonvulsant effect of THPO, a GABA uptake inhibitorGeneral Pharmacology: The Vascular System, 1985
- Transport and Metabolism of 7‐Aminobutyric Acid in Neurons and Glia: Implications for EpilepsyEpilepsia, 1983
- Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPONeuropharmacology, 1983
- Ion dependency of uptake and release of GABA and (RS)‐nipecotic acid studied in cultured mouse brain cortex neuronsJournal of Neuroscience Research, 1983
- Heterocyclic GABA analogues as new selective inhibitors of astroglial GABA transportDrug Development Research, 1981
- Changes in the Uptake of GABA and Taurine During Neuronal and Glial MaturationJournal of Neurochemistry, 1980
- Rat cortical neurons in cell culture: Culture methods, cell morphology, electrophysiology, and synapse formationBrain Research, 1978
- A Modification of Davidon's Minimization Method to Accept Difference Approximations of DerivativesJournal of the ACM, 1967