Two monoclonal antibodies (mAbs) against bovine heparin-binding growth factor II (HBGF-II)/basic fibroblast growth factor (bFGF) were obtained from mouse hybridoma cell lines. They were highly specific for bFGF from bovine, human, and mouse sources and did not cross-react with bovine heparin-binding growth factor I (HBGF-I)/acidic fibroblast growth factor (aFGF). The immunoglobulin class and subclass of these mAbs were IgGI, Kc. The apparent dissociation constant (Kd) for bFGF of these mAbs ranged from 10-9 to 10-10 M. One mAb (bFM-2) also cross-reacted with heat-inactivated bFGF, while the other mAb (bFM-1) did not, suggesting that bFM-1 recognized the conformation of the bFGF molecule necessary for its biological activity. These mAbs inhibited growth of cultured bovine capillary endothelial cells in both the presence and absence of exogenous bFGF, indicating the autocrine action of this growth factor in in vitro growth of these cells. On the other hand, injection of these hybridoma cell lines s.c. into the backs of athymic mice resulted in development of highly vascularized solid tumors and a sustained high level of anti-bFGF activity in the blood of the tumor-bearing mice. These findings suggest that bFGF is not essential as an autocrine or paracrine growth factor for angiogenesis in vivo. These mAbs should be useful in further studies on the physiological role and the conformation-function relationship of bFGF because they block its biological activity.
Linalool is a major component of essential oils and possesses various biological effects in sensory or central nervous systems. To investigate the pharmacological and biophysical effects of linalool on voltage-gated currents in sensory neurons, we used the whole-cell patch clamp and the Ca(2+) imaging techniques. Under the voltage clamp, membrane depolarization generated time- and voltage-dependent current responses in newt olfactory receptor cells (ORCs). Linalool significantly and reversibly suppressed the voltage-gated currents in ORCs. The dose-suppression relation of linalool for the voltage-gated Na(+) current could be fitted by the Hill equation with a half-blocking concentration of 0.56 mM and a Hill coefficient of 1.2. To test whether linalool suppresses voltage-gated currents in ORCs specifically or suppresses currents in other neurons generally, we next examined the effects of linalool on voltage-gated currents in newt retinal neurons and rat cerebellar Purkinje cells. Linalool suppressed the voltage-gated currents not only in retinal horizontal cells and ganglion cells but also in Purkinje cells. Furthermore, bath application of linalool inhibited the KCl-induced [Ca(2+)](i) response of ORCs, suggesting that linalool suppresses Ca(2+) currents in ORCs. These results suggest that linalool non-selectively suppresses the voltage-gated currents in newt sensory neurons and rat cerebellar Purkinje cells.
The finding of an elevated expression of bFGF immunoreactivity in the photocoagulated lesion suggests that bFGF may play a role in wound repair in the rat retina after laser photocoagulation.
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