Potentiation of a behavioural response in mice by spinal coadministration of substance P and excitatory amino acid agonists.
The functional interaction in the spinal cord between substance P and excitatory amino acid agonists was investigated. Behavioural responses were scored in mice after intrathecal administration of excitatory amino acid agonists and substance P, given separately or in combination. A strong potentiation of the effect was seen when substance P was coadministered with N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) or kainic acid (KA). The potentiation was blocked by the corresponding antagonists: the selective NMDA-receptor antagonist (+/-)-3- (2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the substance P analog, [D-Arg1,D-Trp7,9,Leu11]-substance P (Spantide). These findings indicate a functional interaction between substance P and glutamate in the dorsal horn of the spinal cord, compatible with the hypothesis that corelease of substance P and glutamate from primary afferent neurons may enhance nociception.
Mjellem-Joly
N
N
Departement of Physiology, University of Bergen, Norway.
Lund
A
A
Berge
O G
OG
Hole
K
K
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004357:Drug Synergism; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007278:Injections, Spinal; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D000700:Analgesics; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D013373:Substance P; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C042867:spantide; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D007608:Kainic Acid