Nociceptive behavior induced by poly-L-lysine and other basic compounds involves the spinal NMDA receptors.
We have previously shown that spermine, a basic polyamine, and big dynorphin, a basic polypeptide, induce nociceptive behavior if injected intrathecally (i.t.) in mice (see [Pain 86 (2000) 55-61] and [Brain Res. 952 (2002) 7-14]). This suggests that other basic molecules might have the same effects. Here, i.t. administration of poly-L-lysine (12 and 36 pg) to mice was found to produce the same characteristic behavioral response, biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank, which peaked at 0-10 min after injection. The behavior induced by poly-L-lysine (12 pg) was dose-dependently inhibited by intraperitoneal injection of morphine (0.25-4 mg/kg) and also dose-dependently, by i.t. co-administration of D-(-)-2-amino-5-phosphonovaleric acid (D-APV) (1-4 nmol), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine hydrogen maleate (MK-801) (0.0156-4 nmol), an NMDA ion-channel blocker, and ifenprodil (2-8 nmol), an antagonist of the polyamine recognition site and the NR2B-containing NMDA receptor subtype. On the other hand, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA glutamate receptor antagonist, 7-chlorokynurenic acid, a competitive antagonist of the glycine recognition site on the NMDA receptor ion-channel complex, [D-Phe7, d-His9]-substance P (6-11), a specific antagonist for substance P (NK1) receptors, or MEN-10,376, a tachykinin NK2 receptor antagonist, had no effect. These results confirm the observations obtained with other basic molecules and suggest that the behavior induced by poly-l-lysine is mediated through the activation of the NMDA receptor ion-channel complex acting either on the polyamine recognition site or on the NR2B subunit.
Tan-No
Koichi
K
Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. koichi@tohoku-pharm.ac.jp
Esashi
Akihisa
A
Nakagawasai
Osamu
O
Niijima
Fukie
F
Sakurada
Chikai
C
Sakurada
Tsukasa
T
Bakalkin
Georgy
G
Terenius
Lars
L
Tadano
Takeshi
T
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000139:chemically induced*; D010147:Pain Measurement / Q000187:drug effects; D011107:Polylysine / Q000633:toxicity*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D064729:Neurokinin-1 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D011107:Polylysine; D009020:Morphine