Agonist stimulation of B1 and B2 kinin receptors causes activation of the MAP kinase signaling pathway, resulting in the translocation of AP-1 in HEK 293 cells.
In response to bradykinin, phosphorylated MAP kinases (ERK-1 and ERK-2) were abundantly increased in HEK 293 cells, which overexpress the rat B2 kinin receptor. In a similar way des-Arg9-bradykinin stimulation of B1 kinin receptor-overexpressing HEK 293 cells caused activation of the same species of MAP kinase. Furthermore, nuclear translocation of transcription factor AP-1 was also found in the cells after stimulation with either agonist. PD98059, a MAP kinase kinase (MEK-1) inhibitor, blocked the agonist-induced AP-1 translocation as well as the phosphorylation of the MAP kinases. This communication provides the first evidence for both B1 and B2 kinin receptors mediating the MAP kinase signaling pathway to activate AP-1.
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
H
H
Naraba
A
A
Ueno
Y
Y
Kosugi
M
M
Yoshimura
M
M
Murakami
I
I
Kudo
S
S
Oh-ishi
D000818:Animals; D001692:Biological Transport; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D016384:Consensus Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D009841:Oligonucleotides / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists* / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism*
D065168:Bradykinin Receptor Antagonists; D005419:Flavonoids; D009841:Oligonucleotides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D018808:Transcription Factor AP-1; C065679:icatibant; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D001920:Bradykinin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one