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Research ArticleInflammation, Immunopharmacology, and Asthma

Involvement of Extracellular Signal-Regulated Kinase 5 in Kinin B1 Receptor Upregulation in Isolated Human Umbilical Veins

Yael Kilstein, Wanda Nowak, Andrea Emilse Errasti, Antía Andrea Barcia Feás, Arnaldo Raúl Armesto, Facundo Germán Pelorosso and Rodolfo Pedro Rothlin
Journal of Pharmacology and Experimental Therapeutics April 2016, 357 (1) 114-124; DOI: https://doi.org/10.1124/jpet.115.230169
Yael Kilstein
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Wanda Nowak
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Andrea Emilse Errasti
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Antía Andrea Barcia Feás
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Arnaldo Raúl Armesto
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Facundo Germán Pelorosso
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Rodolfo Pedro Rothlin
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Abstract

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-Arg10-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.

Footnotes

    • Received October 21, 2015.
    • Accepted January 8, 2016.
  • This research was supported by grants from Universidad de Buenos Aires (UBA, 20020100100611) and Consejo de Investigaciones Científicas y Técnicas (CONICET, PIP2620), Argentina.

  • dx.doi.org/10.1124/jpet.115.230169.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 357 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 357, Issue 1
1 Apr 2016
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Research ArticleInflammation, Immunopharmacology, and Asthma

ERK5 in Kinin B1 Receptor Upregulation in HUV

Yael Kilstein, Wanda Nowak, Andrea Emilse Errasti, Antía Andrea Barcia Feás, Arnaldo Raúl Armesto, Facundo Germán Pelorosso and Rodolfo Pedro Rothlin
Journal of Pharmacology and Experimental Therapeutics April 1, 2016, 357 (1) 114-124; DOI: https://doi.org/10.1124/jpet.115.230169

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Research ArticleInflammation, Immunopharmacology, and Asthma

ERK5 in Kinin B1 Receptor Upregulation in HUV

Yael Kilstein, Wanda Nowak, Andrea Emilse Errasti, Antía Andrea Barcia Feás, Arnaldo Raúl Armesto, Facundo Germán Pelorosso and Rodolfo Pedro Rothlin
Journal of Pharmacology and Experimental Therapeutics April 1, 2016, 357 (1) 114-124; DOI: https://doi.org/10.1124/jpet.115.230169
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