Involvement of Extracellular Signal-Regulated Kinase 5 in Kinin B1 Receptor Upregulation in Isolated Human Umbilical Veins
| Autor: | Arnaldo Armesto, Antía Andrea Barcia Feás, Rodolfo Pedro Rothlin, Wanda Nowak, Yael Kilstein, Facundo Germán Pelorosso, Andrea Emilse Errasti |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway medicine.medical_specialty Serotonin Umbilical Veins MAP Kinase Signaling System Biology Receptor Bradykinin B1 p38 Mitogen-Activated Protein Kinases Muscle Smooth Vascular 03 medical and health sciences chemistry.chemical_compound Downregulation and upregulation Pregnancy Internal medicine medicine Humans RNA Messenger Protein kinase A Receptor Mitogen-Activated Protein Kinase 7 Janus Kinases Pharmacology Dose-Response Relationship Drug Kinase Kallidin Kinin Cell biology Up-Regulation 030104 developmental biology Endocrinology chemistry Molecular Medicine Female Janus kinase Muscle Contraction |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 357(1) |
| ISSN: | 1521-0103 |
| Popis: | The upregulated kinin B1 receptors exert a pivotal role in modulating inflammatory processes. In isolated human umbilical veins (HUVs), kinin B1 receptor is upregulated as a function of in vitro incubation time and proinflammatory stimuli. The aim of this study was to evaluate, using functional and biochemical methods, the involvement of extracellular signal-regulated kinase 5 (ERK5), p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) on the kinin B1 receptor upregulation process in HUV. Real-time polymerase chain reaction analysis revealed for the first time that kinin B1 receptor mRNA expression closely parallels the functional sensitization to kinin B1 receptor selective agonist des-Arg(10)-kallidin (DAKD) in HUV. Moreover, the selective inhibition of ERK5, p38 MAPK, and JNK, but not ERK1/2, produced a dose-dependent rightward shift of the concentration-response curves to DAKD after 5-hour incubation and a reduction in kinin B1 receptor mRNA expression. Biochemical analyses showed that ERK5, p38 MAPK, and JNK phosphorylation is maximal during the first 2 hours postisolation, followed by a significant reduction in the last 3 hours. None of the treatments modified the responses to serotonin, an unrelated agonist, suggesting a specific effect on kinin B1 receptor upregulation. The present work provides for the first time pharmacologic evidence indicating that ERK5 plays a significant role on kinin B1 receptor upregulation. Furthermore, we confirm the relevance of p38 MAPK and JNK as well as the lack of effect of ERK1/2 in this process. This study may contribute to a better understanding of MAPK involvement in inflammatory and immunologic diseases. |
| Databáze: | OpenAIRE |
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