SUPEROXIDE SCAVENGING EFFECT OF GINKGO-BILOBA EXTRACT ON SEROTONIN-INDUCED MITOGENESIS

We have reported previously that serotonin (5-HT) stimulates the mitog enesis oi bovine pulmonary artery smooth muscle cells (SMCs) through a ctive transport of 5-HT and cellular signaling that includes elevation of superoxide (O-2(.-)) and enhancement of protein tyrosine phosphory lation. Ginkgo biloba extract 501 (EGb 501), which has been demonstrat ed to act as an antioxidant, was found to block both the elevated O-2( .-) and the proliferative and hypertrophic influences of 5-HT on SMCs, but not to directly inhibit the associated activation of NAD(P)H oxid ase or the stimulation of phosphorylation of GTPase-activating protein (GAP). A similar effect of Ginkgo biloba extract 501 occurred on Chin ese hamster lung fibroblasts (CCL-39), where 5-HT receptor, as opposed to transporter, action has been associated with mitogenesis. We concl ude from these studies that Ginkgo biloba extract 501 quenches O-2(.-) formation by 5-HT, thereby blocking its mitogenic effect. Stimulation of protein tyrosine phosphorylation of GAP by 5-HT appears to precede the elevation of O-2(.-). BIOCHEM PHARMACOL 56;4:527-533, 1998. (C) 1 998 Elsevier Science Inc.