1. The Ca 2+ /CaM, Src kinase and/or PI3K-dependent EGFR transactivation via 5-HT 2A and 5-HT 1B receptor subtypes mediates 5-HT-induced vasoconstriction.
- Author
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Guner S, Akhayeva T, Nichols CD, and Gurdal H
- Subjects
- Vasoconstriction physiology, Serotonin pharmacology, Serotonin metabolism, Phosphatidylinositol 3-Kinases metabolism, Receptor, Serotonin, 5-HT1B metabolism, Proto-Oncogene Proteins c-akt metabolism, Transcriptional Activation, Phosphorylation, src-Family Kinases metabolism, ErbB Receptors metabolism
- Abstract
G protein-coupled receptors (GPCR) and receptor tyrosine kinases (RTK) modulate vascular tone and contraction via rapid and long-term processes. Sustained activation of these receptor types can change vascular structure, and the ability of vasculature to adapt to high pressure. In this study, the interaction between serotonin (5-HT) receptors and epidermal growth factor receptors (EGFR) on vasoconstriction and the mechanisms of EGFR transactivation and its downstream mediators were investigated. We measured 5-HT-induced vasoconstriction in the aorta and the mesenteric artery; and the effects of EGFR, Src and PI3K, and their downstream mediators Erk1/2 and Akt phosphorylation on 5-HT-mediated vasoconstriction in the presence or absence of pharmacological inhibitors of Ca
2+ /CaM, EGFR, Src, and PI3K. Furthermore, we determined the contribution of 5-HT receptor subtypes to 5-HT-induced vasoconstriction and EGFR transactivation using selective 5-HT2A and 5-HT1B receptors ligands. Our results show that EGFR, Src, and PI3K are involved in 5-HT-induced vasoconstriction both in the aorta and the mesenteric artery, and that these kinases have a more prominent role in the mesenteric artery than the aorta. With regard to EGFR transactivation by 5-HT, Ca2+ /CaM, Src and PI3K are upstream mediators, and transactivation is partly mediated by Erk1/2 and Akt activation. Furthermore, Ca2+ /CaM, Src, and PI3K are the main regulators for Akt activation, however Src only has a prominent role for Erk1/2 activation. 5-HT2A and 5-HT1B receptors have different EGFR transactivation profiles through Src and/or PI3K, with 5-HT2A having a greater role than 5-HT1B receptors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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