TY - JOUR T1 - Involvement of Extracellular Signal-Regulated Kinase 5 in Kinin B<sub>1</sub> Receptor Upregulation in Isolated Human Umbilical Veins JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 114 LP - 124 DO - 10.1124/jpet.115.230169 VL - 357 IS - 1 AU - Yael Kilstein AU - Wanda Nowak AU - Andrea Emilse Errasti AU - Antía Andrea Barcia Feás AU - Arnaldo Raúl Armesto AU - Facundo Germán Pelorosso AU - Rodolfo Pedro Rothlin Y1 - 2016/04/01 UR - http://jpet.aspetjournals.org/content/357/1/114.abstract N2 - 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. ER -