Peripheral GABA A receptors - Physiological relevance and therapeutic implications.

Autor: Gajić Bojić M; Faculty of Medicine, Center for Biomedical Research, University of Banja Luka, Banja Luka 78000, Republic of Srpska, Bosnia and Herzegovina; Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Banja Luka - Faculty of Medicine, Banja Luka 78000, Republic of Srpska, Bosnia and Herzegovina., Aranđelović J; Department of Pharmacology, University of Belgrade - Faculty of Pharmacy, Belgrade 11000, Serbia., Škrbić R; Faculty of Medicine, Center for Biomedical Research, University of Banja Luka, Banja Luka 78000, Republic of Srpska, Bosnia and Herzegovina; Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Banja Luka - Faculty of Medicine, Banja Luka 78000, Republic of Srpska, Bosnia and Herzegovina., Savić MM; Department of Pharmacology, University of Belgrade - Faculty of Pharmacy, Belgrade 11000, Serbia. Electronic address: miroslav@pharmacy.bg.ac.rs.
Jazyk: angličtina
Zdroj: Pharmacology & therapeutics [Pharmacol Ther] 2024 Nov 28; Vol. 266, pp. 108759. Date of Electronic Publication: 2024 Nov 28.
DOI: 10.1016/j.pharmthera.2024.108759
Abstrakt: The role of γ- aminobutyric acid (GABA) and GABA A receptors is not only essential for neurotransmission in the central nervous system (CNS), but they are also involved in communication in various peripheral tissues such as the pancreas, liver, kidney, gastrointestinal tract, trachea, immune cells and blood vessels. GABA A receptors located outside the CNS ("peripheral GABA A receptors") enable both neuronal and non-neuronal GABA-ergic signaling in various physiological processes and are generally thought to have similar properties to the extrasynaptic receptors in the CNS. By activating these peripheral receptors, GABA and various GABA A receptor modulators, including drugs such as benzodiazepines and general anesthetics, may contribute to or otherwise affect the maintenance of general body homeostasis. However, the existing data in the literature on the role of non-neuronal GABA-ergic signaling in insulin secretion, glucose metabolism, renal function, intestinal motility, airway tone, immune response and blood pressure regulation are far from complete. In fact, they mainly focus on the identification of components for the local synthesis and utilization of GABA and on the expression repertoire of GABA A receptor subunits rather than on subunit composition, activation effects and (sub)cellular localization. A deeper understanding of how modulation of peripheral GABA A receptors can have significant therapeutic effects on a range of pathological conditions such as multiple sclerosis, diabetes, irritable bowel syndrome, asthma or hypertension could contribute to the development of more specific pharmacological strategies that would provide an alternative or complement to existing therapies. Selective GABA A receptor modulators with improved peripheral efficacy and reduced central side effects would therefore be highly desirable first-in-class drug candidates. This review updates recent advances unraveling the molecular components and cellular determinants of the GABA signaling machinery in peripheral organs, tissues and cells of both, humans and experimental animals.
Competing Interests: Declaration of competing interest The authors have no conflicts of interest or competing financial interests to declare that are relevant to the content of this review article. M.M.S. is a co-inventor or listed on patent applications that cover GABAergic ligands and their use in brain disorders, but not in diseases of organ systems other than the nervous system.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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