ArticlebioRxiv : the preprint server for biology2025
Differential effects of sodium on agonist-induced conformational transitions and signaling at μ and κ opioid receptors.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Sodium ions are classically conceptualized as negative allosteric modulators for G protein coupled receptors (GPCRs), although there have been reports of either positive allosteric modulation or no effect of sodium on GPCR function. Here we identified opposing actions of sodium on the μ and κ opioid receptors. We utilized a variety of methods including radioligand binding, real-time conformational monitoring of transitions using bioluminescence resonance energy transfer and signaling assays using the TRUPATH resource. At the μ receptors, sodium behaved as a negative allosteric modulator of binding, conformational transitions and signaling. Intriguingly, bitopic μ agonists were unaffected by sodium concentrations. By contrast, at the κ opioid receptor sodium negatively modulated agonist binding and positively modulated conformational transitions and signaling. Taken together, these findings support the notion that the differential sensitivities to sodium concentrations will result in opposing effects on cell surface and intracellular signaling.
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