Enhancer substances: selegiline and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] enhance the neurotrophic factor synthesis on cultured mouse astrocytes.
R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] is a potent "catecholaminergic and serotonergic activity enhancer (CAE/SAE)", which enhances the impulse-evoked catecholamines and serotonin release, e.g. (-)-BPAP enhances in vitro norepinephrine efflux from the slices of locus coeruleus in a bipolar manner with the two effective ranges of low (fM-pM level) and high (nM-microM level) concentrations. Here, the effects of (-)-BPAP and selegiline on the cultured mouse astrocytes were studied. The protein levels of the neurotrophic factors (NGF, BDNF and GDNF) in the conditioned medium of cultured astrocytes were determined by using ELISA. In the cultured astrocytes incubated for 24 h with selegiline, the synthesis of NGF and BDNF was significantly enhanced in the concentration dependent manner, with minimum effective concentrations of 4 x 10(-4) and 5 x 10(-4) M, respectively. (-)-BPAP also enhanced the NGF, BDNF and GDNF synthesis, with minimum effective concentrations of 5 x 10(-5), 1 x 10(-5), and 1 x 10(-6) M, respectively. Although the effects of (-)-BPAP on the NGF synthesis was tested in the range of 1 x 10(-15)-5 x 10(-4) M, the concentration response curve of (-)-BPAP was a single bell shape with the peak effect at 1 x 10(-4) M, and did not show any effects in low concentrations such as fM-pM level. Each concentration response curve of (-)-BPAP on BDNF and GDNF synthesis was a single bell shape with peak effects at 1 x 10(-3) M and 1 x 10(-4) M, respectively.
Shimazu
Seiichiro
S
Research Institute, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Matsubara, 580-0011, Osaka, Japan. soyaku@fujimoto-pharm.co.jp <soyaku@fujimoto-pharm.co.jp>
Tanigawa
Akie
A
Sato
Noriyuki
N
Yoneda
Fumio
F
Hayashi
Kyozo
K
Knoll
Joseph
J
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001572:Benzofurans / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051379:Mice; D008813:Mice, Inbred ICR; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*
C404200:1-(benzofuran-2-yl)-2-propylaminopentane; D001572:Benzofurans; D019208:Brain-Derived Neurotrophic Factor; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D012642:Selegiline; D001058:Apomorphine