Omeprazole Suppresses Endothelial Calcium Response and eNOS Ser1177 Phosphorylation in Porcine Aortic Endothelial Cells
| Autor: | Akio Hakamata, Ryugo Sakurada, Chiaki Kamiya, Naoki Inui, Hiroshi Watanabe, Keiichi Odagiri |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Nitric Oxide Synthase Type III
Swine Prostaglandin Bradykinin Pharmacology Endoplasmic Reticulum Nitric Oxide Nitric oxide omeprazole chemistry.chemical_compound Enos Genetics medicine Animals Phosphorylation Molecular Biology Aorta Omeprazole calcium Dose-Response Relationship Drug biology Phospholipase C nitric oxide synthase Endoplasmic reticulum endothelium-dependent relaxing factors General Medicine biology.organism_classification Epoprostenol endothelial cells Nitric oxide synthase chemistry biology.protein Endothelium Vascular medicine.drug |
| Zdroj: | Molecular Biology Reports. 48(7):5503-5511 |
| ISSN: | 0301-4851 |
| Popis: | Background Although high doses of proton pump inhibitors can elicit an anticancer effect, this strategy may impair vascular biology. In particular, their effects on endothelial Ca2⁺ signaling and production of endothelium-derived relaxing factor (EDRF) are unknown. To this end, we investigated the effects of high dosages of omeprazole on endothelial Ca2⁺ responses and EDRF production in primary cultured porcine aortic endothelial cells.Methods and Results Omeprazole (10–1000μM) suppressed both bradykinin (BK)- and thapsigargin-induced endothelial Ca2⁺ response in a dose-dependent manner. Furthermore, omeprazole slightly attenuated Ca2⁺ mobilization from the endoplasmic reticulum, whereas no inhibitory effects on endoplasmic reticulum Ca2⁺-ATPase were observed. Omeprazole decreased BK-induced phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and tended to decrease BK-induced nitric oxide production. Production of prostaglandin I₂ metabolites, especially 6-keto-prostaglandin 1α, also tended to be reduced by omeprazole.Conclusion Our results are the first to indicate that high doses of omeprazole may suppress both store-operated Ca2⁺ channels and partially the G protein-coupled receptor/phospholipase C/inositol 1,4,5-triphosphate pathway, and decreased BKinduced, Ca2⁺-dependent phosphorylation of eNOS(Ser1177). Thus, high dosages of omeprazole impaired EDRF production by attenuating intracellular Ca2⁺ signaling. |
| Databáze: | OpenAIRE |
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