NK-3 receptors mediate enhancement of substance P release from capsaicin-sensitive spinal cord afferent terminals

摘要

class="enumerated" style="list-style-type:decimal">The effects of NK-3 receptor agonists on the release of substance P-immunoreactivity (SP-LI) have been investigated using superfused rat spinal cord synaptosomes.The Ca²⁺-dependent overflow of SP-LI evoked by 35 mM KCl was concentration-dependently enhanced by senktide (EC50=52 nM; maximal effect=70%) or [MePhe⁷]NKB (EC50=5.5 nM; maximal effect=125%), both selective agonists at receptors of the NK-3 type.The potentiation of the SP-LI overflow elicited by 100 nM senktide or [MePhe⁷]NKB was prevented by the NK-3 receptor antagonist (+)-SR142801. The antagonist halved, at 10 nM, and almost abolished, at 100 nM, the effect of both agonists. The effect of senktide or [MePhe⁷]NKB was insensitive to antagonists at NK-1 or NK-2 receptors.Capsaicin (0.1–1 μM) stimulated SP-LI release in a concentration-dependent manner from spinal cord synaptosomes. The SP-LI overflow elicited by 1 μM capsaicin was completely dependent on external Ca²⁺. Senktide could not affect the capsaicin-evoked release of SP-LI.Senktide failed to potentiate the K⁺-evoked overflow of SP-LI from synaptosomes previously exposed for 15 min in superfusion to capsaicin.The results show that release-enhancing NK-3 receptors are located on axon terminals of capsaicin-sensitive primary afferent neurones in the spinal cord. Antagonists at NK-3 receptors might help controlling pain transmission.