Prolonged modulation of FGF-2 expression in astrocytic cultures induced by O,O'-diacetyl-apomorphine.
Apomorphine (APO) is an anti-parkinsonian drug currently in use, which provides relief of Parkinson's symptoms. However, the utility of APO is greatly hampered by its poor bioavailability and rapid metabolism. In the present study, O,O'-diacetyl-apomorphine, a prodrug of apomorphine, was synthesized and its biological activity was examined. The prodrug induced fibroblast growth factor-2 production in astrocytic cultures similarly to apomorphine. However, its duration of action was significantly prolonged, and its resistance to oxidation was markedly enhanced compared to APO. O,O'-Diacetyl-apomorphine also induced MEK/MAPK signaling. These results suggest that O,O'-diacetyl-apomorphine can efficiently counteract oxidation and thereby enhance FGF-2 production in astrocytes.
He
Xiaochun
X
Department of Chemical Engineering, Nantong Vocational College, Nantong, JS 226007, China.
Wang
Dakui
D
Zhang
Xinhua
X
Li
Aiqun
A
Gu
Xiaosong
X
Ding
Fei
F
Zhou
Jiawei
J
D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
D000978:Antiparkinson Agents; C528173:O,O'-diacetylapomorphine; D011355:Prodrugs; D016222:Fibroblast Growth Factor 2; D001058:Apomorphine