NK-3 receptors mediate enhancement of substance P release from capsaicin-sensitive spinal cord afferent terminals.
1. 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. 2. 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. 3. 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. 4. Capsaicin (0.1-1 microM) stimulated SP-LI release in a concentration-dependent manner from spinal cord synaptosomes. The SP-LI overflow elicited by 1 microM capsaicin was completely dependent on external Ca2+. Senktide could not affect the capsaicin-evoked release of SP-LI. 5. Senktide failed to potentiate the K+-evoked overflow of SP-LI from synaptosomes previously exposed for 15 min in superfusion to capsaicin. 6. 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.
Schmid
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G
Department of Experimental Medicine, University of Genoa, Italy.
Carità
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F
Bonanno
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Raiteri
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D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018042:Receptors, Neurokinin-3 / Q000819:agonists* / Q000187:drug effects; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects
D018042:Receptors, Neurokinin-3; D013373:Substance P; D002211:Capsaicin