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. 2025 Aug 1;26(15):7459. doi: 10.3390/ijms26157459

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© 2025 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Cellular mechanism of action of opioid receptors. Binding of an opioid agonist to the µ-opioid receptor activates Gi/o protein signaling, leading to inhibition of adenylyl cyclase and a subsequent decrease in intracellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity. This results in reduced phosphorylation of intracellular proteins. Concurrently, opioid receptor activation inhibits voltage-gated calcium channels (reducing excitatory neurotransmitter release) and opens potassium channels, causing membrane hyperpolarization. These combined effects lead to reduced neuronal excitability and diminished synaptic transmission. +: activation; −: inhibition. Created in BioRender. Ruiz de Porras, V. (2025). https://BioRender.com/bx6zmb5.