| Summary: | In this study, we examined whether aortic contraction, induced by the alpha‐2 adreno-ceptor agonist dexmedetomidine, is involved in the transactivation of the epidermal growth factor receptor (EGFR) in isolated endothelium‐denuded rat aortas. Additionally, we aimed to elucidate the associated underlying cellular mechanisms. The effects of the alpha‐2 adrenoceptor inhibitor rauwolscine, EGFR tyrosine kinase inhibitor AG1478, Src kinase inhibitors PP1 and PP2, and matrix metalloproteinase inhibitor GM6001 on EGFR tyrosine phosphorylation and c‐Jun NH2‐terminal kinase (JNK) phosphorylation induced by dexmedetomidine in rat aortic smooth muscles were ex-amined. In addition, the effects of these inhibitors on dexmedetomidine‐induced contraction in isolated endothelium‐denuded rat aorta were examined. Dexmedetomidine‐induced contraction was inhibited by the alpha‐1 adrenoceptor inhibitor prazosin, rauwolscine, AG1478, PP1, PP2, and GM6001 alone or by a combined treatment with prazosin and AG1478. AG1478 (3 × 10−6 M) inhibited dexmedetomidine‐induced contraction in isolated endothelium‐denuded rat aortas pretreated with rauwolscine. Dexmedetomidine‐induced EGFR tyrosine and JNK phosphorylation were inhibited by rauwolscine, PP1, PP2, GM6001, and AG1478. Furthermore, dexmedetomidine‐induced JNK phosphorylation reduced upon EGFR siRNA treatment. Therefore, these results suggested that the transactivation of EGFR associated with dexmedetomidine‐induced contraction, mediated by the alpha‐2 adrenoceptor, Src kinase, and matrix metalloproteinase, caused JNK phosphorylation and increased calcium levels. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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