Jcg. Marvizon et al., Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABA(B) receptors, EUR J NEURO, 11(2), 1999, pp. 417-426
Inhibitory amino acids have antinociceptive actions in the spinal cord that
may involve inhibition of neurotransmitter release from primary afferents.
Rat spinal cord slices with dorsal roots were used to study the effect of
GABA and glycine on substance P release, assessed by the internalization of
neurokinin 1 receptors. After electrical stimulation of the dorsal root at
100 Hz, about half of neurokinin 1 receptor-immunoreactive neurons in lami
nae I-IIo showed internalization. This internalization was inhibited by GAB
A (100 mu M) and the GABA(B) agonist R-baclofen (10 mu M), but not by the G
ABA(A) agonist muscimol (20 mu M) or glycine (100 mu M). The GABA(B) antago
nist 2-hydroxysaclofen (100 mu M) reversed the inhibitory effect of GABA, b
ut not the GABA(A) antagonist bicuculline (100 mu M), These findings demons
trate that GABA(B) receptors, but not GABA(A) or glycine receptors, inhibit
substance P release induced by dorsal root stimulation. In contrast, R-bac
lofen did not inhibit the internalization produced by NMDA (100 mu M), indi
cating that the stimulatory effect of NMDA receptors on substance P release
is able to surmount the inhibitory effect of GABA(B) receptors. In the pre
sence of the GABA(B) antagonist 2-hydroxysaclofen (100 mu M), but not in it
s absence, stimulation of the dorsal root at 1 or 10 Hz was able to elicit
internalization, which was not inhibited by the NMDA receptor antagonist AP
-5 (50 mu M) or the channel blocker MK-801 (10 mu M). Therefore, inhibition
of substance P release by GABA(B) receptors is tonic, and in its absence S
P release no longer requires NMDA receptor activation.