rho(1) GABA(C) receptor antagonists inhibit myopia in chick but the site of this effect is not known. The sclera ultimately determines the shape and size of the globe and thus an untested possibility is that GABA agents have a scleral mechanism. Whether rho(1) GABA(C) receptors are expressed and located in chick sclera is unknown. Real-time PCR, western blot and immunohistochemistry were used to determine whether rho1 GABA(C) receptors are expressed and located in chick fibrous and cartilaginous sclera. Both layers of the chick sclera were positive for rho1 GABA(C) receptor mRNA (PCR) and protein (western blot) expression and labeling was observed in both fibroblasts and chondrocytes of the fibrous and cartilaginous layers (immunohistochemistry). These investigations clearly show that chick sclera possesses rho(1) GABA(C) receptors. The sclera is thus a potential previously unrecognized site for activity of rho(1) GABA(C) agents.
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http://dx.doi.org/10.1111/j.1471-4159.2011.07300.x | DOI Listing |
IUPHAR BPS Guide Pharm CITE
September 2021
Medical University Vienna, Austria.
The GABA receptor is a ligand-gated ion channel of the Cys-loop family that includes the nicotinic acetylcholine, 5-HT and strychnine-sensitive glycine receptors. GABA receptor-mediated inhibition within the CNS occurs by fast synaptic transmission, sustained tonic inhibition and temporally intermediate events that have been termed 'GABA, slow' [45]. GABA receptors exist as pentamers of 4TM subunits that form an intrinsic anion selective channel.
View Article and Find Full Text PDFBrain Sci
March 2021
Brain and Mind Centre, School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Ischemic stroke remains a leading cause of disability worldwide, with limited treatment options available. This study investigates GABA receptors as novel pharmacological targets for stroke recovery. The expression of 1 and 2 mRNA in mice were determined in peri-infarct tissue following photothrombotic motor cortex stroke.
View Article and Find Full Text PDFNeuropharmacology
October 2018
Division of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. Electronic address:
GABA and GABA receptors are both GABA-gated chloride channels with distinct pharmacological properties, mainly in their sensitivity to bicuculline and gabazine. In this study, we found that suramin, a purinergic receptor antagonist, is a novel competitive antagonist selective to GABA over GABA receptors. Specifically, suramin antagonized the GABA-induced current and the spontaneous opening current of the wild type α1β2γ2 GABA receptor with high-level expression in Xenopus oocytes.
View Article and Find Full Text PDFChemMedChem
October 2016
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
The ρ-containing γ-aminobutyric acid type A receptors (GABA Rs) play an important role in controlling visual signaling. Therefore, ligands that selectively target these GABA Rs are of interest. In this study, we demonstrate that the partial GABA R agonist imidazole-4-acetic acid (IAA) is able to penetrate the blood-brain barrier in vivo; we prepared a series of α- and N-alkylated, as well as bicyclic analogues of IAA to explore the structure-activity relationship of this scaffold focusing on the acetic acid side chain of IAA.
View Article and Find Full Text PDFPLoS One
July 2017
Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
The loop C hydrophilic residue, threonine 244 lines the orthosteric binding site of ρ1 GABAC receptors was studied by point mutation into serine, alanine and cysteine, and tested with GABA, some representative partial agonists and antagonists. Thr244 has a hydroxyl group essential for GABA activity that is constrained by the threonine methyl group, orienting it toward the binding site. Significant decreases in activation effects of the studied ligands at ρ1 T244S mutant receptors, suggests a critical role for this residue.
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