Signalling pathways involved in the short-term potentiation of dopamine release by BDNF.
Brain-derived neurotrophic factor (BDNF) has been shown to modulate synaptic plasticity in the corpus striatum in vitro by activation of the tyrosine kinase linked receptor, TrkB. However, the signalling pathways that mediate this modulation of plasticity are poorly understood. Three proteins mediating signalling pathways are activated by the binding of BDNF to TrkB: phosphoinositol-3 kinase (PI3K); Ras-MEK and phospholipase C-gamma (PLCgamma). The present study investigates which of these pathways are necessary for BDNF-mediated potentiation of synaptic output of dopamine from slices and synaptosomes of rat corpus striatum. The results indicate that activation of the PI3K and Ras-MEK pathways, but not PLCgamma, are involved. Inhibitors of transcription and translation had no effect on the potentiation of depolarisation-stimulated (15 mM KCl) dopamine release mediated by BDNF.
Goggi
Julian
J
Department of Biochemistry, Imperial College of Science, Technology and Medicine, Imperial College Road, South Kensington, SW7 2AY, London, UK
Pullar
Ian A
IA
Carney
Stephen L
SL
Bradford
Henry F
HF
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D008562:Membrane Glycoproteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic; D020813:Receptor, trkB
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D002867:Chromones; D004298:Dopamine; D004791:Enzyme Inhibitors; D005419:Flavonoids; D026121:Indole Alkaloids; D008562:Membrane Glycoproteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D011189:Potassium Chloride; D011505:Protein-Tyrosine Kinases; D011994:Recombinant Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C049985:staurosporine aglycone; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one