By using a series of aminocyclopentane- and aminocyclohexanecarboxylic acids, as well as some naturally occurring amino acids, it was possible to determine some aspects of the spatial topography of the GABA membrane binding and transport sites. The NA-independent GABA binding site was found to have a different spatial topography than the Na-dependent binding site in that trans-3-aminocyclopentanecarboxylic acid (trans-3-ACPC) was 7 times more potent than cis-3-ACPC to inhibit Na-independent binding, but only 1.6 times more potent to inhibit Na-dependent binding. The nerve ending GABA transport site was found to be similar to the Na-dependent GABA binding site in that it will accommodate both cis- and trans-3-ACPC. However, the transport site differs from the binding site in that cis-3-aminocyclohexanecarboxylic acid (cis-3-ACHC) is a potent inhibitor of transport but a weak inhibitor of binding. In addition to the differences in spatial characteristics, differences in the subcellular distribution of Na-independent and Na-dependent binding sites were observed. The former were found primarily in the nerve ending-mitochondrial fraction, while the latter were primarily found in the microsomal fraction.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/0006-8993(78)90435-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanistic insights into HPV-positivity in non-smokers and HPV-negativity in smokers with head and neck cancer.
Front Oncol
January 2025
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Introduction: Several aspects of the involvement of HPV in the pathogenesis of HPV-associated diseases remain poorly understood including mechanistic aspects of infection and the question of why the majority of HPV-positive HNSCC-patients are non-smokers, whereas HPV-negatives are smokers. Our previous research, based on 1,100 patient samples, hypothesized an explanation for this phenomenon: Smoking induces upregulation of a mucosal protective protein (SLPI), which competes with HPV for binding to Annexin A2 (AnxA2), pivotal for HPV cell entry. Here we investigate the mechanistic aspects of our hypothesis using transfection assays.
View Article and Find Full Text PDFMachine learning and molecular dynamics simulations predict potential TGR5 agonists for type 2 diabetes treatment.
Front Chem
January 2025
African Society for Bioinformatics and Computational Biology, Cape Town, South Africa.
Introduction: Treatment of type 2 diabetes (T2D) remains a significant challenge because of its multifactorial nature and complex metabolic pathways. There is growing interest in finding new therapeutic targets that could lead to safer and more effective treatment options. Takeda G protein-coupled receptor 5 (TGR5) is a promising antidiabetic target that plays a key role in metabolic regulation, especially in glucose homeostasis and energy expenditure.
View Article and Find Full Text PDFCoordinated regulation of two LacI family regulators, GvmR and GvmR2, on guvermectin production in .
Synth Syst Biotechnol
November 2024
Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Northeast Agricultural University, Harbin, 150030, China.
Guvermectin, a purine nucleoside natural product produced by the genus S, has recently been registered as a new biopesticide to boost rice yield. Despite its economic and agricultural significance, the regulatory mechanisms of guvermectin biosynthesis remain essentially unknown, hindering industrial production and widespread agricultural application. Here, we examined the roles of two LacI family regulators, and , located within and adjacent to the guvermectin biosynthesis cluster, respectively, in guvermectin production in NEAU6.
View Article and Find Full Text PDFComputer-assisted discovery of natural inhibitors for platelet-derived growth factor alpha as novel therapeutics for thyroid cancer.
Front Pharmacol
January 2025
Department of Biochemistry, Bahauddin Zakariya University, Multan, Pakistan.
Platelet-derived growth factor alpha (PDGFRA) plays a significant role in various malignant tumors. PDGFRA expression boosts thyroid cancer cell proliferation and metastasis. Radiorefractory thyroid cancer is poorly differentiated, very aggressive, and resistant to radioiodine therapy.
View Article and Find Full Text PDFProbing structural requirements for thiazole-based mimetics of sunitinib as potent VEGFR-2 inhibitors.
RSC Med Chem
January 2025
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University Mansoura 35516 Egypt
Novel thiazole analogs 3a, 3b, 4, 5, 6a-g, 8a, 8b, 9a-c, 10a-d and 11 were designed and synthesized as molecular mimetics of sunitinib. antitumor activity of the obtained compounds was investigated against HepG2, HCT-116, MCF-7, HeP-2 and HeLa cancer cell lines. The obtained data showed that compounds 3b and 10c are the most potent members toward HepG2, HCT-116, MCF-7 and HeLa cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!