The effects of substance P analogues on the scratching, biting and licking response induced by intrathecal injection of N-methyl-D-aspartate in mice.
1. Intrathecal (i.t.) administration of N-methyl-D-aspartate (NMDA) elicited a dose-dependent behavioural response consisting of licking, biting and scratching in mice. 2. Repeated i.t. injections of 0.4 nmol NMDA, at 5 min intervals, resulted in the rapid development of desensitization to this NMDA-induced behavioural phenomenon. 3. The NMDA-induced response was dose-dependently inhibited by the simultaneous injection of a selective NMDA-receptor antagonist, D-2-amino-5-phosphonovaleric acid. 4. The substance P (SP) analogues [D-Pro2, D-Trp7,9] SP and [D-Arg1, D-Trp7,9, Leu11] SP (spantide) inhibited NMDA-induced behavioural responses in a dose-dependent manner. However, [D-Phe7, D-His9] SP (6-11), a SP analogue selective for neurokinin1 (NK1) receptors, failed to inhibit NMDA-induced responses even at a dose of 4.0 nmol. 5. These results indicate that NMDA-induced behavioural responses are mainly mediated through NMDA receptors without affecting NK1 receptors in the spinal cord.
Department of Pharmacology, Tohoku College of Pharmacy, Aoba-ku, Japan.
T
T
Sakurada
Y
Y
Manome
K
K
Tan-No
S
S
Sakurada
K
K
Kisara
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007278:Injections, Spinal; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000700:Analgesics; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; C032292:substance P (6-11); D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C032132:substance P, prolyl(2)-tryptophan(7,9)-; C042867:spantide; D011761:Pyrrolidonecarboxylic Acid