Spinal calmodulin inhibitors reduce N-methyl-D-aspartate- and septide-induced nociceptive behavior.
The effect of two calmodulin inhibitors, W-7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide) and calmidazolium, on the nociceptive behavior induced by the intrathecal injection of NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid) or of septide is described. Lumbar intrathecal injection of NMDA, AMPA or septide induced a caudally directed nociceptive reaction (biting, scratching and licking). The nociceptive behavior induced by NMDA (4 microg) was dose dependently inhibited when W-7 (0.25-1 micromol/rat) or calmidazolium (0.12-0.5 micromol/rat) was coinjected. Biting, scratching and licking produced by AMPA (2 microg) were unaffected by intrathecal calmodulin inhibitors. Finally, septide-evoked nociceptive behavior (2 microg) was antagonized by W-7 (0.12-0.5 micromol/rat) and calmidazolium (0.06-0.25 micromol/rat). Thus, calmodulin inhibitors prevent the nociceptive reaction evoked by drugs that modify intracellular Ca2+, NMDA and septide, without affecting the nociceptive response induced by AMPA, for which Ca2+ is not the main second messenger.
Menéndez
L
L
Departamento de Medicina, Facultad de Medicina, Oviedo, Asturias, Spain.
Hidalgo
A
A
Baamonde
A
A
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015288:Neurokinin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000737:chemistry*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000494:pharmacology
D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D013449:Sulfonamides; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; C031938:calmidazolium; D016202:N-Methylaspartate; C017967:W 7; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C054725:septide; D015288:Neurokinin A; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D011761:Pyrrolidonecarboxylic Acid