dc.contributor.author | Guner, Sahika | |
dc.contributor.author | Akhayeva, Tamila | |
dc.contributor.author | Nichols, Charles D. | |
dc.contributor.author | Gurdal, Hakan | |
dc.date.accessioned | 2023-11-16T18:30:00Z | |
dc.date.available | 2023-11-16T18:30:00Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 0006-2952 | |
dc.identifier.issn | 1873-2968 | |
dc.identifier.uri | https://doi.org/10.1016/j.bcp.2022.115317 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14065/5553 | |
dc.description.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) re-ceptors 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 pharmaco-logical inhibitors of Ca2+/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. | en_US |
dc.description.sponsorship | TUBITAK; [111S131] | en_US |
dc.description.sponsorship | Grant: This study was granted by TUBITAK (Project No: 111S131) . | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Pergamon-Elsevier Science Ltd | en_US |
dc.relation.ispartof | Biochemical Pharmacology | en_US |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | 5-Ht Receptor Subtypes | en_US |
dc.subject | Egfr | en_US |
dc.subject | Transactivation | en_US |
dc.subject | Vascular Smooth Muscle | en_US |
dc.subject | Epidermal-Growth-Factor | en_US |
dc.subject | Smooth-Muscle-Cells | en_US |
dc.subject | Tyrosine Kinase | en_US |
dc.subject | Angiotensin-Ii | en_US |
dc.subject | C-Src | en_US |
dc.subject | Phosphatidylinositol 3-Kinase | en_US |
dc.subject | Regulated Kinase | en_US |
dc.subject | Rat Aorta | en_US |
dc.subject | Activation | en_US |
dc.subject | Contraction | en_US |
dc.title | The Ca2+/CaM, Src kinase and/or PI3K-dependent EGFR transactivation via 5-HT2A and 5-HT1B receptor subtypes mediates 5-HT-induced vasoconstriction | en_US |
dc.type | article | en_US |
dc.authorid | Nichols, Charles D/0000-0002-0615-0646 | |
dc.authorid | Guner, Sahika/0000-0002-5171-4287 | |
dc.authorid | Akhayeva, Tamila/0000-0003-1929-4494 | |
dc.department | Ufuk Üniversitesi | en_US |
dc.identifier.doi | 10.1016/j.bcp.2022.115317 | |
dc.identifier.volume | 206 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.authorwosid | Nichols, Charles D/F-7153-2012 | |
dc.authorwosid | Akhayeva, Tamila/C-1811-2017 | |
dc.identifier.wos | WOS:000890781900006 | en_US |
dc.identifier.pmid | 36374715 | en_US |