Inflammation-induced release of excitatory amino acids is prevented by spinal administration of a GABAA but not by a GABAB receptor antagonist in rats.
After the injection of kaolin and carrageenan into the knee joint of rats, there was a decrease in paw withdrawal latency (PWL) to radiant heat ipsilaterally, which indicates hyperalgesia. This decrease was blocked by pretreatment of the spinal cord dorsal horn with the gamma-aminobutyric acid (GABAA) receptor antagonist, bicuculline but not with the GABAB receptor antagonist, CGP35348, administered by microdialysis. The inflammation-induced release of amino acids from the spinal dorsal horn occurred in two phases: 1) an early phase at the time of injection and 2) a late phase at 3.5 to 8 hr. The amino acids released in the late phase included aspartate (ASP), glutamate (GLU) and glutamine. During the PWL test, there was also the release of the inhibitory amino acids, serine and glycine, after the induction of arthritis. The increased release of excitatory amino acids at the time of injection was unaffected by pretreatment with either bicuculline or CGP35348. The release of amino acids during the late phase and during the PWL test was blocked by pretreatment with bicuculline but not CGP35348. The increase in joint circumference typical of this model did not occur with pretreatment with the GABAA receptor antagonist. The change in joint circumference was positively correlated with the late phase release of ASP and GLU. In bicuculline-treated arthritic animals in which joint inflammation was minimal, concentrations of ASP and GLU did not increase above base line.
Marine Biomedical Institute, University of Texas Medical Branch, Galveston.
K A
KA
Sluka
W D
WD
Willis
K N
KN
Westlund
D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D001640:Bicuculline / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism*; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
D018846:Excitatory Amino Acids; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D001224:Aspartic Acid; D018698:Glutamic Acid; C066430:CGP 35348; D001640:Bicuculline