Sl. Lee et al., Serotonin stimulates mitogen-activated protein kinase activity through theformation of superoxide anion, AM J P-LUNG, 21(2), 1999, pp. L282-L291
Citations number
47
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Our previous studies have shown that, through an active transport process,
serotonin (5-HT) rapidly elevates O-2(-.) formation, stimulates protein pho
sphorylation, and enhances proliferation of bovine pulmonary artery smooth
muscle cells (SMCs). We presently show that 1 mu M 5-HT also rapidly elevat
es phosphorylation and activation of the mitogen-activated protein (MAP) ki
nases extracellular signal-regulated kinase (ERK) 1 and ERK2 of SMCs, and t
he enhanced phosphorylation is blocked by the antioxidants Tiron, N-acetyl-
L-cysteine (NAC), and Ginkgo biloba extract. inhibition of MAP kinase with
PD-98059 failed to block enhanced O-2(-.) formation by 5-HT. Chinese hamste
r lung fibroblasts (CCL-39 cells), which demonstrate both 5-HT transporter
and receptor activity, showed a similar response to 5-HT (i.e., enhanced mi
togenesis, O-2(-.) formation, and ERK1 and ERK2 phosphorylation and activat
ion). Unlike SMCs,they also responded to 5-HT receptor agonists. We conclud
e that downstream signaling of MAP kinase is a generalized cellular respons
e to 5-HT that occurs secondary to O-2(-.) formation and may be initiated b
y either the 5-HT transporter or receptor depending on the cell type.