TY - JOUR
T1 - The mitogen-activated protein kinase p38-2 is necessary for the inhibition of N-type calcium current by bradykinin
AU - Wilk-Blaszczak, Malgorzata A.
AU - Stein, Bernd
AU - Xu, Shuichan
AU - Barbosa, Miguel S.
AU - Cobb, Melanie H.
AU - Belardetti, Francesco
PY - 1998
Y1 - 1998
N2 - Calcium influx via voltage-dependent calcium channels (I(Ca,V)) links depolarization of excitable cells to critical cellular processes, such as secretion, contraction, and gene transcription. Fast regulation of I(Ca,V) (<1 sec) by G-protein-coupled receptors is a relatively well-defined mechanism, whereas slow (30-60 sec) actions of transmitters and hormones on the same current remain poorly understood. In NG108-15 cells, the kinetically slow inhibition of N-type I(Ca,V) by bradykinin (BK) requires the sequential activation of two G-proteins, heterotrimeric G13 and monomeric Rac1/Cdc42. We have now defined a role in this pathway for the relatively fast-acting p38 mitogen-activated protein kinase (MAPK). The slow inhibition of I(Ca,V) by BK was suppressed specifically by SB203580, a compound that inhibits the p38 family of MAPKs. BK potently and selectively activated a newly discovered p38 family member, p38-2. These data provide the first evidence that a MAPK is involved in the regulation of I(Ca,V) by a receptor-mediated process.
AB - Calcium influx via voltage-dependent calcium channels (I(Ca,V)) links depolarization of excitable cells to critical cellular processes, such as secretion, contraction, and gene transcription. Fast regulation of I(Ca,V) (<1 sec) by G-protein-coupled receptors is a relatively well-defined mechanism, whereas slow (30-60 sec) actions of transmitters and hormones on the same current remain poorly understood. In NG108-15 cells, the kinetically slow inhibition of N-type I(Ca,V) by bradykinin (BK) requires the sequential activation of two G-proteins, heterotrimeric G13 and monomeric Rac1/Cdc42. We have now defined a role in this pathway for the relatively fast-acting p38 mitogen-activated protein kinase (MAPK). The slow inhibition of I(Ca,V) by BK was suppressed specifically by SB203580, a compound that inhibits the p38 family of MAPKs. BK potently and selectively activated a newly discovered p38 family member, p38-2. These data provide the first evidence that a MAPK is involved in the regulation of I(Ca,V) by a receptor-mediated process.
KW - Bradykinin
KW - Calcium channels
KW - G
KW - G-protein
KW - MAPK
KW - NG108-15
KW - Neuroblastoma x glioma
KW - p38
UR - http://www.scopus.com/inward/record.url?scp=0031963773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031963773&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.18-01-00112.1998
DO - 10.1523/jneurosci.18-01-00112.1998
M3 - Article
C2 - 9412491
AN - SCOPUS:0031963773
SN - 0270-6474
VL - 18
SP - 112
EP - 118
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 1
ER -