SR 57746A attenuates cytostatic drug-induced reduction of neurite outgrowth in co-cultures of rat dorsal root ganglia and Schwann cells.
A co-culture system of intact rat dorsal root ganglia (DRG) with Schwann cells was used to evaluate the potential neurotrophic activity of SR 57746A. Neuritogenesis from DRG was measured with an image analysis system following exposure to different concentrations of SR 57746A. Neurite outgrowth of intact DRG was increased by SR 57746A and this was more obvious in the presence of co-cultured Schwann cells. The neuroprotective properties of SR 57746A were studied in co-cultures of DRG and Schwann cells, in which neuritogenesis was reduced by the cytostatic drugs cisplatin, vincristine and taxol. It was found that neurite outgrowth from DRG treated with cisplatin (3 micrograms/ml) and 10 microM SR 57746A for 3 days was significantly higher than after treatment with cisplatin alone. Similarly, neuritogenesis from DRG treated with taxol (0.01 microgram/ml) or vincristine (0.5 ng/ml) in combination with 10 microM SR 57746A was significantly increased compared to treatment with taxol or vincristine alone. When intact DRG were incubated in vitro with 3 micrograms/ml cisplatin and without Schwann cells, 10 microM SR 57746A also had a neuroprotective effect. These data suggest that SR 57746A has neuroprotective potential and that this effect does not depend solely on the presence of Schwann cells.
Ruigt
G S
GS
Neuropharmacology Department, NV Organon, Netherlands.
Makkink
W K
WK
Konings
P N
PN
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D012583:Schwann Cells / Q000187:drug effects*; D012584:Sciatic Nerve / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D009281:Naphthalenes; D011725:Pyridines; D017366:Serotonin Receptor Agonists; D002945:Cisplatin; C462299:xaliproden