Interactions between excitatory amino acids and tachykinins in the rat spinal dorsal horn.
Whole-cell patch-clamp technique of freshly isolated rat spinal dorsal horn (DH) neurons, intracellular recording from DH neurons in a slice preparation, and high performance liquid chromatography with fluorimetric detection of release of endogenous glutamate and aspartate from spinal cord slice following activation of primary afferent fibers were employed to investigate interactions between excitatory amino acids (EAA) and tachykinins [substance P (SP) and neurokinin A (NKA)]. Potentiation of N-methyl-D-aspartate (NMDA)-, quisqualate (QA)- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-, but not kainate-induced currents by SP and NKA was found. Spantide II, a claimed novel nonselective tachykinin antagonist, effectively blocked the SP (2 nM)-induced potentiation of the responses of DH neurons to NMDA. In the presence of glycine (0.1 microM), the SP-evoked increase of the NMDA-induced current was prevented. However, 7-chlorokynurenic acid (2 microM), a competitive antagonist at the glycine allosteric site of the NMDA receptor, led to the reestablishment of the SP effect. Brief high frequency electrical stimulation of primary afferent fibers produced a long-lasting potentiation of presumed monosynaptic and polysynaptic excitatory postsynaptic potentials and sustained enhanced release of endogenous glutamate (218.3 +/- 66.1%) and aspartate (286.3 +/- 58.0%). Possible functional implications of the observed phenomena are discussed in relation to transmission and integration of sensory information, including pain.
Rusin
K I
KI
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
Jiang
M C
MC
Cerne
R
R
Randic
M
M
D000344:Afferent Pathways / Q000187:drug effects; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000596:Amino Acids; D017459:Receptors, Amino Acid; D015320:Tachykinins; C065446:spantide II; D013373:Substance P; D005998:Glycine