Competitive Antagonism of Xylazine on α7 Nicotinic Acetylcholine Receptors and Reversal by Curcuminoids.

ABSTRACT: Co-use of xylazine with opioids is a major health threat in the United States. However, a critical knowledge gap exists in the understanding of xylazine-induced pharmacological and pathological impact. Xylazine is mostly known as an agonist of α2-adrenergic receptors (α2-ARs), but its deleterious effects on humans cannot be fully reversed by the α2-AR antagonists, suggesting the possibility that xylazine targets receptors other than α2-ARs. Here, we report the discovery of α7 nicotinic acetylcholine receptors (α7 nAChRs) as targets of xylazine. In Xenopus oocytes expressing α7 nAChRs, xylazine competitively antagonizes channel currents elicited by the agonist acetylcholine. In PC12 cells, xylazine suppresses choline-stimulated intracellular calcium ([Ca²⁺]_in) t

SUBMITTER: Chen Q 

PROVIDER: S-EPMC11741004 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature