Apomorphine induces trophic factors that support fetal rat mesencephalic dopaminergic neurons in cultures.
Apomorphine, the catechol-derived dopamine D1/D2 receptor agonist, is currently in use as an antiparkinsonian drug. It has previously been reported that apomorphine was able to elicit expression of the enzyme tyrosine hydroxylase, a marker for DA neurons, in the fetal rat cerebrocortical cultures whilst in the presence of brain-derived neurotrophic factor. The present study demonstrated that treatment of fetal rat ventral mesencephalic cultures with apomorphine caused a marked increase in the number of dopaminergic neurons. The action of apomorphine can be mimicked by dopamine receptor (D1 and D2) agonists or blocked by preincubation with D1/D2 receptor antagonists. Incubation of recipient mesencephalic cultures with the conditioned medium derived from apomorphine-stimulated donor mesencephalic cultures elicited a 3.72-fold increase in the number of TH-positive neurons. Increased mRNA expression levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor were also found in the apomorphine-treated mesencephalic cells along with concomitant protein expression increases in the conditioned medium. Moreover, the trophic activity observed could be partially neutralized by antibodies against either brain-derived neurotrophic factor or glial cell line-derived neurotrophic factor. Cultured fetal striatal cells, but not hippocampal cells, also responded to apomorphine treatment. The membrane filtration studies revealed that both <30 kDa and >50 kDa fractions contained trophic activities. The latter characterization distinguishes them from most known neurotrophic factors. These results suggest that the apomorphine-modulated development of dopaminergic neurons may be mediated by activation of the dopamine receptor subtypes D1 and D2 thereby increasing the production of multiple growth factors.
Guo
Hong
H
Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China.
Tang
Zhongshu
Z
Yu
Yi
Y
Xu
Lei
L
Jin
Guozhang
G
Zhou
Jiawei
J
D000818:Animals; D001058:Apomorphine / Q000378:metabolism / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002452:Cell Count; D018929:Cell Culture Techniques; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006220:Haloperidol / Q000494:pharmacology; D008636:Mesencephalon / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013134:Spiperone / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001552:Benzazepines; D019208:Brain-Derived Neurotrophic Factor; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine