Allosteric modulation of G protein-coupled receptors by amiloride and its derivatives. Perspectives for drug discovery?

ABSTRACT: The function of G protein-coupled receptors (GPCRs) can be modulated by compounds that bind to other sites than the endogenous orthosteric binding site, so-called allosteric sites. Structure elucidation of a number of GPCRs has revealed the presence of a sodium ion bound in a conserved allosteric site. The small molecule amiloride and analogs thereof have been proposed to bind in this same sodium ion site. Hence, this review seeks to summarize and reflect on the current knowledge of allosteric effects by amiloride and its analogs on GPCRs. Amiloride is known to modulate adenosine, adrenergic, dopamine, chemokine, muscarinic, serotonin, gonadotropin-releasing hormone, GABA_B , and taste receptors. Amiloride analogs with lipophilic substituents tend to be more potent modulators tha

SUBMITTER: Massink A 

PROVIDER: S-EPMC7028016 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature