Indirect actions of bradykinin on neonatal rat dorsal root ganglion neurones: a role for non-neuronal cells as nociceptors.
1. In this study we have investigated the action of bradykinin (Bk) on cultured neonatal rat dorsal root ganglion (DRG) cells, with the aim of elucidating whether the neuronal response to Bk is influenced by association with non-neuronal satellite cells. 2. Bradykinin (100 nM) evoked an inward current (I(Bk)) in 51 of 58 voltage clamped DRG neurones (holding potential (V(h)) = -80 mV) that were in contact with non-neuronal satellite cells. 3. Bradykinin failed to evoke an inward current in isolated DRG neurones (V(h) = -80 mV) that were not in contact with non-neuronal satellite cells (n = 41). 4. The lack of neuronal response to Bk was not influenced by time in culture. Bradykinin failed to evoke a response in isolated neurones through 1-5 days in culture. By contrast neurones in contact with satellite cells responded to Bk throughout the same time period. 5. Failure of isolated neurones to respond to Bk was not due to the replating procedure or to selective subcellular distribution of receptors/ion channels to the processes rather than the somata of neurones. 6. Using Indo-1 AM microfluorimetry Bk (100 nM) was demonstrated to evoke an intracellular Ca(2+) increase (Ca(Bk)) in DRG neurones in contact with non-neuronal satellite cells and in isolated neurones. 7. These data suggest that the inward current response to Bk requires contact between DRG neurones and non-neuronal satellite cells. This implies an indirect mechanism of action for Bk via the non-neuronal cells, which may perform a nociceptive role. However, Bk can also act directly on the neurones, since it evokes Ca(Bk) in isolated neurones. The relationship between Ca(Bk) and the Bk-induced inward current is unknown at present.
Heblich
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F
Centre for Neuroscience, Sensory Function, Hodgkin Building, King's College London, Guy's Campus, London SE1 1UL, UK.
England
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S
Docherty
R J
RJ
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology*; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009619:Nociceptors / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027161:Satellite Cells, Perineuronal / Q000166:cytology / Q000502:physiology; D013997:Time Factors
D009467:Neuromuscular Depolarizing Agents; C012301:domoic acid; D011188:Potassium; D001920:Bradykinin; D007608:Kainic Acid; D002118:Calcium