Acute and late effects on induction of allodynia by acromelic acid, a mushroom poison related structurally to kainic acid.

Abstract

1. Ingestion of a poisonous mushroom Clitocybe acromelalga is known to cause severe tactile pain (allodynia) in the extremities for a month and acromelic acid (ACRO), a kainate analogue isolated from the mushroom, produces selective damage of interneurons of the rat lower spinal cord when injected either systemically or intrathecally. Since ACRO has two isomers, ACRO-A and ACRO-B, here we examined their acute and late effects on induction of allodynia. 2. Intrathecal administration of ACRO-A and ACRO-B provoked marked allodynia by the first stimulus 5 min after injection, which lasted over the 50-min experimental period. Dose-dependency of the acute effect of ACRO-A on induction of allodynia showed a bell-shaped pattern from 50 ag x kg(-1) to 0.5 pg x kg(-1) and the maximum effect was observed at 50 fg x kg(-1). On the other hand, ACRO-B induced allodynia in a dose-dependent manner from 50 pg x kg(-1) to 50 ng x kg(-1). 3. N-methyl-d-aspartate (NMDA) receptor antagonists and Joro spider toxin, a Ca(2+)-permeable AMPA receptor antagonist, inhibited the allodynia induced by ACRO-A, but not by ACRO-B. However, other AMPA/kainate antagonists did not affect the allodynia induced by ACRO. 4. Whereas no neuronal damage was observed in the spinal cord in ACRO-A-treated mice, induction of allodynia by ACRO-A (50 fg x kg(-1)) and ACRO-B (50 ng x kg(-1)) was selectively lost 1 week after i.t. injection of a sublethal dose of ACRO-A (50 ng x kg(-1)) or ACRO-B (250 ng x kg(-1)). Higher doses of ACRO-A, however, could evoke allodynia dose-dependently from 50 pg x kg(-1) to 500 ng x kg(-1) in the ACRO-A-treated mice. The allodynia induced by ACRO-A (500 ng x kg(-1)) was not inhibited by Joro spider toxin or NMDA receptor antagonists. These properties of the late allodynia induced by ACRO-A were quite similar to those of the acute allodynia induced by ACRO-B. 5. ACRO-A could increase [Ca(2+)](i) in the deeper laminae, rather than in the superficial laminae, of the spinal cord. This increase was not blocked by the AMPA-preferring antagonist GYKI52466 and Joro spider toxin. 6. Taken together, these results demonstrate the stereospecificity of ACRO for the induction of allodynia and suggest the presence of a receptor specific to ACRO.

• Authors: Toshiaki Minami, Shinji Matsumura, Mikio Nishizawa, Yasuyuki Sasaguri, Nobuyuki Hamanaka, Seiji Ito
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 142 Issue 4 Pg. 679-88 (Jun 2004) ISSN: 0007-1188 [Print] England
• PMID: 15159282 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Heterocyclic Compounds
• Indoles
• JSTX spider toxin
• Oximes
• Quinoxalines
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• Spider Venoms
• 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
• Benzodiazepines
• 5-nitro-6,7,8,9-tetrahydrobenzo(G)indole-2,3-dione-3-oxime
• 4-methylglutamic acid
• Nerisopam
• Dizocilpine Maleate
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
• acromelic acid A
• Kainic Acid
• acromelic acid B

Topics

• Animals
• Basidiomycota (chemistry, isolation & purification)
• Benzodiazepines (pharmacology)
• Dizocilpine Maleate (pharmacology)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical (methods)
• Glutamates (pharmacology)
• Heterocyclic Compounds (administration & dosage, adverse effects)
• Indoles (pharmacology)
• Injections, Spinal
• Japan
• Kainic Acid (administration & dosage, adverse effects, analogs & derivatives, antagonists & inhibitors, chemistry)
• Lumbosacral Region (injuries, pathology)
• Male
• Mice
• Mice, Inbred Strains
• Mushroom Poisoning (complications)
• Oximes (pharmacology)
• Pain (chemically induced, complications, prevention & control)
• Quinoxalines (pharmacology)
• Receptors, AMPA (administration & dosage, antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (administration & dosage, antagonists & inhibitors)
• Spider Venoms (pharmacology)
• Spinal Cord (drug effects, pathology, ultrastructure)
• Stereoisomerism
• Structure-Activity Relationship
• Time Factors
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (pharmacology)