Bradykinin B1 receptor expression induced by tissue damage in the rat portal vein: a critical role for mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways.
The bradykinin B1 receptor (B1R) is normally absent under physiological conditions, but is highly inducible during inflammatory conditions or following tissue damage. The present study attempted to determine some of the mechanisms underlying B1R upregulation following tissue injury in rat portal vein. Damage induced by tissue isolation and in vitro incubation caused a significant and time-dependent increase in des-Arg9-bradykinin (des-Arg9-BK) responsiveness that paralleled the B1R mRNA expression, as confirmed by real-time quantitative PCR. In vitro incubation of rat portal vein also induced the activation of some members of the mitogen activated protein kinase (MAPK) family, namely, extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAPK, an effect accompanied by degradation of the inhibitory protein IkappaBalpha and translocation of nuclear transcription factor-kappaB (NF-kappaB) to the nucleus. The blockade of p38 MAPK, JNK or NF-kappaB, but not ERK pathways with selective inhibitors, resulted in a significant reduction of the upregulated contractile response caused by the selective B1R agonist des-Arg9-BK, and largely prevented the induction of B1R mRNA expression in the rat portal vein. Together, these results demonstrate that in vitro tissue damage induces activation of several intracellular signaling pathways that have a key role in the control of B1R expression. B1R could exert a pivotal role in the development of the cardiovascular response associated with vascular damage.
Medeiros
Rodrigo
R
Department of Pharmacology, Universidade Federal de Santa Catarina, Brazil.
Cabrini
Daniela A
DA
Ferreira
Juliano
J
Fernandes
Elizabeth S
ES
Mori
Marcelo A S
MA
Pesquero
João B
JB
Bader
Michael
M
Avellar
Maria C W
MC
Campos
Maria M
MM
Calixto
João B
JB
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011169:Portal Vein / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043783:Receptor, Bradykinin B1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; C024626:bradykinin, des-Arg(9)-; D020928:Mitogen-Activated Protein Kinases; D001920:Bradykinin