Intrathecal histamine induces spinally mediated behavioral responses through tachykinin NK1 receptors.
Intrathecal injection of histamine elicited a behavioral response consisting of scratching, biting and licking in conscious mice. Here, we have examined the involvement of substance P (SP) by using intrathecal injection of tachykinin neurokinin (NK)(1) receptor antagonists and SP antiserum. Histamine-induced behavioral response was evoked significantly 5-10 min after intrathecal injection and reached a maximum at 10-15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 200 to 3200 pmol, and maximum effect was observed at 800-1000 pmol. The H(1) receptor antagonist, d-chlorpheniramine and pyrilamine but not the H(2) receptor antagonists, ranitidine and zolantidine, inhibited histamine-induced behavioral response. The NK(1) receptor antagonists, CP-99,994, RP-67580 and sendide, inhibited histamine-induced behavioral response in a dose-dependent manner. A significant antagonistic effect of [D-Phe(7), D-His(9)]SP (6-11), a selective antagonist for SP receptors, was observed against histamine-induced response. The NK(2) receptor antagonist, MEN-10376, had no effect on the response elicited by histamine. Pretreatment with SP antiserum resulted in a significant reduction of the response to histamine. No significant reduction of histamine-induced response was detected in mice pretreated with NK A antiserum. The present results suggest that elicitation of scratching, biting and licking behavior induced by intrathecal injection of histamine may be largely mediated by NK(1) receptors via H(1) receptors in the spinal cord.
Sakurada
Shinobu
S
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. s-sakura@tohoku-pharm.ac.jp
Orito
Tohru
T
Furuta
Seiichi
S
Watanabe
Hiroyuki
H
Mobarakeh
Jalal Izadi
JI
Yanai
Kazuhiko
K
Watanabe
Takehiko
T
Sato
Takumi
T
Onodera
Kenji
K
Sakurada
Chikai
C
Sakurada
Tsukasa
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D054833:Isoindoles; D008297:Male; D051379:Mice; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C523357:substance P (6-11), Phe(7)-His(9)-; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C032292:substance P (6-11); D006632:Histamine; D015288:Neurokinin A; D011761:Pyrrolidonecarboxylic Acid