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Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABA B receptors
Author(s) -
Marvizón Juan Carlos G.,
Grady Eileen F.,
Stefani Enrico,
Bunnett Nigel W.,
Mayer Emeran A.
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00445.x
Subject(s) - ionotropic effect , bicuculline , chemistry , agonist , gabaa receptor , substance p , receptor , stimulation , muscimol , internalization , nmda receptor , inhibitory postsynaptic potential , glycine receptor , pharmacology , receptor antagonist , antagonist , endocrinology , biology , glycine , biochemistry , neuropeptide , amino acid
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 laminae I–II o showed internalization. This internalization was inhibited by GABA (100 μ m ) and the GABA B agonist R‐baclofen (10 μ m ), but not by the GABA A agonist muscimol (20 μ m ) or glycine (100 μ m ). The GABA B antagonist 2‐hydroxysaclofen (100 μ m ) reversed the inhibitory effect of GABA, but not the GABA A antagonist bicuculline (100 μ m ). These findings demonstrate that GABA B receptors, but not GABA A or glycine receptors, inhibit substance P release induced by dorsal root stimulation. In contrast, R‐baclofen did not inhibit the internalization produced by NMDA (100 μ m ), indicating that the stimulatory effect of NMDA receptors on substance P release is able to surmount the inhibitory effect of GABA B receptors. In the presence of the GABA B antagonist 2‐hydroxysaclofen (100 μ m ), but not in its 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 μ m ) or the channel blocker MK‐801 (10 μ m ). Therefore, inhibition of substance P release by GABA B receptors is tonic, and in its absence SP release no longer requires NMDA receptor activation.