G. Schmid et al., NK-3 RECEPTORS MEDIATE ENHANCEMENT OF SUBSTANCE-P RELEASE FROM CAPSAICIN-SENSITIVE SPINAL-CORD AFFERENT TERMINALS, British Journal of Pharmacology, 125(4), 1998, pp. 621-626
1 The effects of NK-3 receptor agonists on the release of substance P-
immunoreactivity (SP-LI) have been investigated using superfused rat s
pinal 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 [MePhe(7)]NKB (EC50 = 5.5 nM; maxim
al effect = 125%), both selective agonists at receptors of the NK-3 ty
pe. 3 The potentiation of the SP-LI overflow elicited by 100 nM senkti
de or [MePhe7]NKB was prevented by the NK-3 receptor antagonist(+)-SR1
42801. The antagonist halved, at 10 nM, and almost abolished, at 100 n
M, 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 mu M) stimulated SP-LI release in a concentration-dependent man
ner from spinal cord synaptosomes. The SP-LI overflow elicited by 1 mu
M capsaicin was completely dependent on external Ca2+. Senktide could
not affect the capsaicin-evoked release of SP-LI. 5 Senktide failed t
o potentiate the K+-evoked overflow of SP-LI from synaptosomes previou
sly exposed for 15 min in superfusion to capsaicin. 6 The results show
that release-enhancing NK-3 receptors are located on axon terminals o
f capsaicin-sensitive primary afferent neurones in the spinal cord. An
tagonists at NK-3 receptors might help controlling pain transmission.