Article date: October 1994
By: Marzia Malcangio, Norman G. Bowery, in Volume 113, Issue 2, pages 635-641
The effects of the non‐peptide tachykinin NK1 receptor antagonists, RP 67580, SR 140333, CP‐96,345 and CP‐99,994 have been investigated on electrically‐evoked release of substance P‐like immunoreactivity (SP‐LI) from rat spinal cord slices.
RP 67580 (10 nm) and SR 140333 (1 nm), perfused 5 min prior to and during 8 min stimulation of the dorsal roots (20 V, 0.5 ms, 1 Hz), significantly enhanced SP‐LI release by 213 ± 43 (n = 8) and 203 ± 31 (n = 5) % of control evoked release (187 ± 16% of basal outflow, n = 22) respectively. Neither compound modified basal outflow of SP‐LI (15.3 ± 2.5 fmol/8 ml, n = 10).
RP 67580 (10 nm) did not modify electrically‐evoked release of calcitonin gene‐related peptide‐LI from rat spinal cord slices.
CP‐96,345 (10 nm) and CP‐99,994 (1 and 10 nm) did not alter electrically‐evoked SP‐LI release; however, they both inhibited release at 1 μm. Inhibition was also induced by 1 μm RP 67580 but not 1 μm SR 140333.
The effect of the NK1 receptor agonists, [Sar9Met (O2)11]SP and [Sar9]SP, could not be tested on SP‐LI release due to interference with the substance P radioimmunoassay (RIA). The other NK1 receptor agonists used, GR 73632, [Pro9]SP and septide, which did not interfere with the RIA, increased SP‐LI basal outflow by 1807 ± 713% (n = 3), 1259 ± 160% (n = 3) and 620 ± 69% (n = 3) at 10 nm, 1 nm and 1 μm, respectively. At the same concentrations, the three agonists also enhanced electrically‐evoked SP‐LI release by 204 ± 38% (n = 6), 753 ± 40% (n = 3) and 504 ± 97% (n = 3), respectively. The GR 73632 (10 nm)‐induced increase in electrically‐evoked SP‐LI release, was not prevented by SR 140333 (100 nm). None of the agonists inhibited SP‐LI release at lower concentrations (0.1 nm GR 73632; 0.01 and 0.1 nm [Pro9]SP and 1–100 nm septide).
NKA and NKB, at concentrations up to 10 nm which did not interfere with the RIA, did not modify electrically‐evoked release of SP‐LI.
The ability of NK1 receptor antagonists to enhance electrically‐evoked SP‐LI release supports the concept of an NK1 autoreceptor control mechanism at substance P nerve terminals within the dorsal horn of the rat spinal cord.
The effects of the non‐peptide tachykinin NK1 receptor antagonists, RP 67580, SR 140333, CP‐96,345 and CP‐99,994 have been investigated on electrically‐evoked release of substance P‐like immunoreactivity (SP‐LI) from rat spinal cord slices.
RP 67580 (10 nm) and SR 140333 (1 nm), perfused 5 min prior to and during 8 min stimulation of the dorsal roots (20 V, 0.5 ms, 1 Hz), significantly enhanced SP‐LI release by 213 ± 43 (n = 8) and 203 ± 31 (n = 5) % of control evoked release (187 ± 16% of basal outflow, n = 22) respectively. Neither compound modified basal outflow of SP‐LI (15.3 ± 2.5 fmol/8 ml, n = 10).
RP 67580 (10 nm) did not modify electrically‐evoked release of calcitonin gene‐related peptide‐LI from rat spinal cord slices.
CP‐96,345 (10 nm) and CP‐99,994 (1 and 10 nm) did not alter electrically‐evoked SP‐LI release; however, they both inhibited release at 1 μm. Inhibition was also induced by 1 μm RP 67580 but not 1 μm SR 140333.
The effect of the NK1 receptor agonists, [Sar9Met (O2)11]SP and [Sar9]SP, could not be tested on SP‐LI release due to interference with the substance P radioimmunoassay (RIA). The other NK1 receptor agonists used, GR 73632, [Pro9]SP and septide, which did not interfere with the RIA, increased SP‐LI basal outflow by 1807 ± 713% (n = 3), 1259 ± 160% (n = 3) and 620 ± 69% (n = 3) at 10 nm, 1 nm and 1 μm, respectively. At the same concentrations, the three agonists also enhanced electrically‐evoked SP‐LI release by 204 ± 38% (n = 6), 753 ± 40% (n = 3) and 504 ± 97% (n = 3), respectively. The GR 73632 (10 nm)‐induced increase in electrically‐evoked SP‐LI release, was not prevented by SR 140333 (100 nm). None of the agonists inhibited SP‐LI release at lower concentrations (0.1 nm GR 73632; 0.01 and 0.1 nm [Pro9]SP and 1–100 nm septide).
NKA and NKB, at concentrations up to 10 nm which did not interfere with the RIA, did not modify electrically‐evoked release of SP‐LI.
The ability of NK1 receptor antagonists to enhance electrically‐evoked SP‐LI release supports the concept of an NK1 autoreceptor control mechanism at substance P nerve terminals within the dorsal horn of the rat spinal cord.
DOI: 10.1111/j.1476-5381.1994.tb17037.x
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