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 Ca 2+ or the addition of Cd 2+ , 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 EC 50 of 30 n m . These responses were not antagonized by the BK 1 selective antagonist Leu 8 des‐Arg 9 BK, but were antagonized by d ‐Arg 0 Hyp 3 Thi 5,8 D‐Phe 7 BK with a pA 2 of 6.8 ± 0.6, which is similar to the values determined for other BK 2 ‐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 Ca 2+ , 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 BK 2 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.