Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABA(B) receptors

Citation
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
Citations number
44
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EUROPEAN JOURNAL OF NEUROSCIENCE
ISSN journal
0953816X → ACNP
Volume
11
Issue
2
Year of publication
1999
Pages
417 - 426
Database
ISI
SICI code
0953-816X(199902)11:2<417:SPRITD>2.0.ZU;2-D
Abstract
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.