In order to explore the molecular interaction between cyclothiazide (CTZ) and gamma-aminobutyric acidA (GABAA) receptors, possibly underlying inhibition of GABAA receptor currents, [3H]-CTZ was synthesized. Binding of [3H]-CTZ to rat brain synaptic membranes could be observed only in the presence of the GABAA receptor antagonist (-)[1S,9R]-bicuculline methiodide (BMI) (EC(50,BMI)=500+/-80microM). GABA decreased [(3)H]-CTZ binding induced by the presence 300microM and 3mM BMI with IC(50,GABA) values of 300+/-50microM and 5.0+/-0.7mM, respectively. Binding of CTZ to [3H]-CTZ labeled sites was characterized by IC(50,CTZ) values of 0.16+/-0.03muM ([BMI]=300microM) and 7.0+/-0.5microM ([BMI]=3mM). Binding of the diastereomeric fraction [3H]-(3R,1'S,4'S,5'R+3S,1'R,4'R,5'S)-CTZ induced by 3mM BMI was quantitatively the more significant in cerebrocortical and hippocampal membranes. It was characterized by IC(50,CTZ)=80+/-15nM and IC(50,GABA)=13+/-3mcapital EM, Cyrillic. In the absence of BMI, CTZ (1mM) significantly decreased GABA-induced enhancement of [3H]-flunitrazepam binding. Our findings suggest that functional inhibition may occur through binding of CTZ to an allosteric site of GABAA receptors. This allosteric site is possibly emerged in the receptor conformation, stabilized by BMI binding.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neulet.2008.04.092 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Involvement of γ-Aminobutyric Acid and N-methyl-D-aspartate Receptors in Diabetic Gastropathy in Rats: Possible Beneficial Effect of Prolonged Treatment with Insulin and Magnesium Supplement.
Arch Razi Inst
June 2024
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Gastrointestinal dysfunction is a severe and common complication in diabetic patients. Some evidence shows that gamma-aminobutyric acid (GABA) and glutamate contribute to diabetic gastrointestinal abnormalities. Therefore, we examined the impact of prolonged treatment with insulin and magnesium supplements on the expression pattern of GABA type A (GABA-A), GABA-B, and N-methyl-D-aspartate (NMDA) glutamate receptors as well as nitric oxide synthase 1 (NOS-1) in the stomach of type 2 diabetic rats.
View Article and Find Full Text PDFCannabichromene from full-spectrum hemp extract exerts acute anti-seizure effects through allosteric activation of GABA receptors.
Fundam Res
November 2024
State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
The approval of Epidiolex, an anti-epileptic drug containing cannabidiol (CBD) as its active component, has brought hope to patients with refractory epilepsy. However, the anti-seizure effect of full-spectrum hemp extract (HE), a CBD-enriched hemp oil, remains unclear. In this study, we investigated the anti-seizure effect of HE using drug-induced seizure models.
View Article and Find Full Text PDFIntervention effect of regulating GABA-A receptor activity on the formation of experimental abdominal aortic aneurysm in rats.
Sci Rep
December 2024
Department of Clinical Medicine, North Sichuang Medical College, Nanchong, 63700, Sichuan Province, China.
Abdominal aortic aneurysm is a potentially fatal vascular inflammatory disease characterized by infiltration of various inflammatory cells.The GABA-A receptor is expressed in many inflammatory cells such as macrophages and T cells and has anti-inflammatory and antioxidant effects. Therefore, the GABA-A receptor may become a potential therapeutic target for abdominal aortic aneurysms.
View Article and Find Full Text PDFAngiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors.
Neuropharmacology
December 2024
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, ul. Mickiewicza 2A, 15-222 Białystok, Poland.
Although angiotensin 1-7 (Ang 1-7) and its role as a part of the "protective" axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1-7 and antagonists for glutamate, GABA, vasopressin, thromboxane A (TP), α-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats.
View Article and Find Full Text PDFInteraction Between Allopregnanolone and Amiloride Binding Sites on the GABA Receptor.
Cell Biochem Biophys
December 2024
Research Center of Neurology, Moscow, Russia.
Allopregnanolone (Allo) is a positive allosteric modulator of the GABA receptor, and amiloride (Ami) is a competitive antagonist of the GABA receptor. The purpose of this work was to study the combined effect of Allo and Ami on functional activity of GABA receptor. The GABA-induced chloride current (I) was measured in isolated Purkinje cells of rat cerebellum using the patch-clamp technique and a system of fast application.
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!