Modulation of N-methyl-D-aspartate and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) responses of spinal nociceptive neurons by a N-terminal fragment of substance P.
The effects of an N-terminal fragment of substance P, substance P-(1-7) [SP-(1-7)], on the responses of dorsal horn nociceptive neurons to N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) were tested by combined single-unit extracellular recordings/microiontophoresis. While SP-(1-7) had no effects when applied by itself, it was a potent and long-lasting modulator of both NMDA- and AMPA-mediated excitation of spinal dorsal horn nociceptive neurons. NMDA responses were transiently decreased (by an average of 36% of control at minimum) by SP-(1-7) followed by a more sustained increase (by 76% at maximum). In contrast, AMP responses were only increased by SP-(1-7) (by 81% at maximum). It is hypothesized that the actions of SP-(1-7) on excitatory amino acid (EAA) responses of dorsal horn nociceptive neurons reflect a novel mechanism by which SP and EAAs interact to modulate pain transmission.
Budai
D
D
Department of Veterinary Pathobiology, University of Minnesota College of Veterinary Medicine, St. Paul 55108.
Wilcox
G L
GL
Larson
A A
AA
D000818:Animals; D004347:Drug Interactions; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D010446:Peptide Fragments; D007051:Ibotenic Acid; D013373:Substance P; D016202:N-Methylaspartate; C036877:substance P (1-7); D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid