Bradykinin-induced depolarization of primary afferent nerve terminals in the neonatal rat spinal cord in vitro.
1. Application of bradykinin (BK) to the spinal cord of the neonatal rat evoked depolarizations which could be recorded via either the dorsal or ventral roots. However, responses recorded via the ventral root were abolished by removal of extracellular Ca2+ or the addition of Cd2+, while responses recorded via the dorsal root were unaffected. 2. The response recorded via the ventral root was inhibited by the substance P antagonist spantide, while responses recorded via the dorsal root were unaffected. 3. Depolarizations recorded via the dorsal root were concentration-dependent with an EC50 of 30 nM. These responses were not antagonized by the BK1 selective antagonist Leu8des-Arg9BK, but were antagonized by D-Arg0Hyp3Thi5,8D-Phe7BK with a pA2 of 6.8 +/- 0.6, which is similar to the values determined for other BK2-mediated responses. 4. Application of phorbol dibutyrate (PDBu) to the spinal cord also evoked a depolarization with respect to the dorsal root. This response to PDBu was enhanced by removal of extracellular Ca2+, while the response to BK was unaffected. 5. The potent protein kinase inhibitor staurosporine reduced the response to PDBu, but did not affect the response to BK. 6. These results suggest that BK by acting on BK2 receptors can depolarize the central terminals of primary afferent nerve fibres. This response to BK does not appear to be mediated via the activation of protein kinase C. The depolarization to BK recorded via the ventral root of the spinal cord is indirect and may be secondary to the action of BK on the primary afferent terminals.
Dunn
P M
PM
Sandoz Institute for Medical Research, London.
Rang
H P
HP
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001665:Binding Sites / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D066298:In Vitro Techniques; D009411:Nerve Endings / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents; D009475:Neurons, Afferent / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects
D009467:Neuromuscular Depolarizing Agents; D002104:Cadmium; D015240:Phorbol 12,13-Dibutyrate; D002211:Capsaicin; D001920:Bradykinin; D002118:Calcium