The role of neurokinin and N-methyl-D-aspartate receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro.
The rat spinal cord with connected dorsal root ganglia was used to study neurokinin and N-methyl-D-aspartate receptors involved in the sensory synaptic transmission of dorsal horn cells. Selective C-fibre excitation was produced by capsaicin (200-500 nM) administered to the dorsal root ganglions. Sixty-nine per cent of dorsal horn cells responded with a postsynaptic depolarization and enhanced synaptic activity, recorded via intracellular electrodes, to capsaicin-activated primary afferent input. Dorsal horn neurons activated by the capsaicin-evoked input were also excited by a 1-min perfusion of the neurokinin-1 receptor agonists substance P methyl ester or GR73 632 and by the neurokinin-2 agonist neurokinin-A. These cells were also depolarized by N-methyl-D-aspartate. Responses to substance P methyl ester and GR73 632 were selectively reduced by the neurokinin-1 receptor antagonist CP96,345, and responses to neurokinin-A were completely blocked by the neurokinin-2 receptor antagonist MEN10 376. The depolarization evoked by N-methyl-D-aspartate was not altered by either of the antagonists, but was completely blocked by the selective N-methyl-D-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid. Capsaicin-evoked responses in the dorsal horn were inhibited by MEN10,376 (63 +/- 13% inhibition) but no significant change was observed with CP96,345. The N-methyl-D-aspartate receptor antagonist (-)-2-amino-5-phosphonovaleric acid consistently inhibited the capsaicin-induced response by 76 +/- 14%. Combination of (-)-2-amino-5-phosphonovaleric acid and MEN10,376 produced an almost complete abolition of the capsaicin-evoked depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Nagy
I
I
Department of Anatomy, University Medical School, Debrecen, Hungary.
Maggi
C A
CA
Dray
A
A
Woolf
C J
CJ
Urban
L
L
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D001713:Biphenyl Compounds; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C068032:GR 73632; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D015288:Neurokinin A; D002211:Capsaicin; C066892:CP 96345