Bradykinin-induced phosphoinositide-dependent responses in protein kinase C down-regulated NCB-20 cells.
Long-term (12 h) incubation of NCB-20 neuroblastoma x Chinese hamster brain cell hybrid cells with phorbol dibutylate caused a decrease in the enzyme activity of protein kinase C (PKC). Under these conditions, the formation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] and the mobilization of intracellular Ca(2+) triggered by bradykinin (BK), were significantly increased. The alterations in BK-triggered membrane currents in the PKC down-regulated cells were also observed: enhancement of outward currents and decreased inward currents. These results strongly suggested that down-regulation of PKC enhanced BK-induced phosphoinositide metabolism by relieving from the negative feedback control operating between the receptor and phospholipase C, and that the increased Ca(2+) responses due to accumulated Ins(1,4,5)P(3) lead to enhanced outward currents.
Okano
Y
Y
Department of Biochemistry, Gifu University School of Medicine, Tsukasamachi 40 Gifu, 500, Japan.
Higashida
H
H
Tao
F
F
Sakai
T
T
Nozawa
Y
Y