title: NMDA receptor activation modulates evoked release of substance P from rat spinal cord.
abstract: The possible modulation exerted by glutamate on substance P (SP) release from the rat spinal cord has been investigated. The N-methyl-D-aspartate (NMDA) receptor agonist, NMDA (1 microM), increased SP basal outflow by 46.5+/-10.9% (n = 3, P<0.01) without changing the evoked release of the peptide. Conversely, NMDA antagonists but not 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited both electrically-evoked and capsaicin-induced release of SP. In particular, D-2-amino-5-phosphonopentanoate (D-AP5; 50 microM) inhibited electrically-evoked and capsaicin-induced release of SP by 93+/-2.4% and 93.2+/-3.8% (n = 12, P<0.01), respectively. Functional pharmacological evidence is provided for glutamate exerting a positive feedback on SP release evoked by C fibre stimulation via NMDA receptor activation.
authors.affiliation: Department of Pharmacology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College.
authors.forename: M
authors.initials: M
authors.lastname: Malcangio
authors.forename: K
authors.initials: K
authors.lastname: Fernandes
authors.forename: D R
authors.initials: DR
authors.lastname: Tomlinson
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D002211:Capsaicin