Glutamate release from adult primary sensory neurons in culture is modulated by growth factors.
The aim of this study was to examine possible modulatory effects of some trophic molecules, i.e. nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF), on potassium (K(+))-, bradykinin (BK)- or capsaicin (CAPS)-evoked release of glutamate (GLU) from dorsal root ganglion (DRG) neurons in vitro. BK (0.5 and 1 microM) induced a dramatic and significant increase in glutamate release. Neither CAPS nor K(+) (60 mM) produced any significant increase of GLU release vs. basal levels during a 5-min stimulation. The BK-evoked release of GLU was almost completely blocked by HOE 140, a selective BK2-receptor antagonist at high doses. Basal release of GLU was significantly reduced in cultures grown in the presence of bFGF, whereas BDNF and NGF had no significant effect. Incubation with growth factors generally decreased the BK-stimulated GLU release, an effect most pronounced for bFGF, which completely blocked BK-stimulated release. The rise in intracellular [Ca(2+)] following stimulation with BK (100 nM-1 microM), potassium (60 mM) or ATP (10 microM) was also studied using a Ca(2+)-sensitive indicator, Fura-2, in cultures grown in basal medium with or without bFGF. None of the bFGF-treated cells exhibited strong Ca(2+) responses to BK or ATP stimulation, while 10-20% of the responding cells grown in basal medium exhibited strong responses. The K(+)-induced increase of [Ca(2+)] did not vary between the different groups. The present findings suggest that sensory neurotransmission involving glutamate may be modulated by growth factors and that regulation of intracellular Ca(2+) homeostasis may be a contributing factor.
Rydh-Rinder
M
M
AstraZeneca, S-151 85 Södertälje, Sweden.
Kerekes
N
N
Svensson
M
M
Hökfelt
T
T
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D018698:Glutamic Acid / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D020932:Nerve Growth Factor / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000166:cytology
D019208:Brain-Derived Neurotrophic Factor; D006133:Growth Substances; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid; D020932:Nerve Growth Factor; D011188:Potassium; D002211:Capsaicin; D001920:Bradykinin; D002118:Calcium