An experimental arthritis model in rats: the effects of NMDA and non-NMDA antagonists on aspartate and glutamate release in the dorsal horn.
Release of excitatory amino acids (EAA's) in the dorsal horn of awake rats was monitored by microdialysis during the development of arthritis induced by injection of 3% kaolin and 3% carrageenan into the knee joint. Concentrations of EAA's in the dialysate samples were measured by high performance liquid chromatography at baseline, during delivery of EAA antagonists, and for the first 8 h of arthritis. An initial increase in aspartate (ASP) and glutamate (GLU) was observed on injection of the knee joint in rats made arthritic. Subsequently, there was a prolonged release phase after 3 h which persisted at least 8 h. Specific EAA antagonists to non-N-methyl-D-aspartate (non-NMDA; CNQX) and to NMDA (AP7) receptors were used to block the effects seen in the untreated arthritic animals. The increase in ASP and GLU release seen at the time of injection in untreated arthritic animals did not occur in arthritic animals treated with EAA receptor antagonists (CNQX or AP7). In arthritic animals treated with CNQX, the prolonged release phase was delayed and attenuated for GLU and decreased below baseline for ASP. In the AP7-treated arthritic animals, no change from baseline concentration was observed for ASP until 7 h, and GLU decreased minimally. The data indicate that this arthritis model is accompanied by an initial increased release of EAA's at the time of injection which is dependent on the activation of both non-NMDA and NMDA receptors. Subsequent development of arthritis, manifested as an inflamed joint and a delayed and prolonged release of ASP and GLU, is dependent on the initial activation of these EAA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Sluka
K A
KA
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 7755-0843.
Westlund
K N
KN
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism*; D002351:Carrageenan; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007270:Injections, Intra-Articular; D007616:Kaolin; D007719:Knee Joint; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*
D000596:Amino Acids; D005971:Glutamates; D011810:Quinoxalines; D007616:Kaolin; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D002351:Carrageenan; C031231:2-amino-7-phosphonoheptanoic acid