TY - JOUR
T1 - Intrathecal histamine induces spinally mediated behavioral responses through tachykinin NK1 receptors
AU - Sakurada, Shinobu
AU - Orito, Tohru
AU - Furuta, Seiichi
AU - Watanabe, Hiroyuki
AU - Mobarakeh, Jalal Izadi
AU - Yanai, Kazuhiko
AU - Watanabe, Takehiko
AU - Sato, Takumi
AU - Onodera, Kenji
AU - Sakurada, Chikai
AU - Sakurada, Tsukasa
PY - 2003/1
Y1 - 2003/1
N2 - 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 H1 receptor antagonist, d-chlorpheniramine and pyrilamine but not the H2 receptor antagonists, ranitidine and zolantidine, inhibited histamine-induced behavioral response. The NK1 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-Phe7, D-His9]SP (6-11), a selective antagonist for SP receptors, was observed against histamine-induced response. The NK2 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 NK1 receptors via H1 receptors in the spinal cord.
AB - 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 H1 receptor antagonist, d-chlorpheniramine and pyrilamine but not the H2 receptor antagonists, ranitidine and zolantidine, inhibited histamine-induced behavioral response. The NK1 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-Phe7, D-His9]SP (6-11), a selective antagonist for SP receptors, was observed against histamine-induced response. The NK2 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 NK1 receptors via H1 receptors in the spinal cord.
KW - Histamine H receptor
KW - NK receptor
KW - Nociceptive response
KW - Substance P
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U2 - 10.1016/S0091-3057(02)01031-6
DO - 10.1016/S0091-3057(02)01031-6
M3 - Article
C2 - 12479971
AN - SCOPUS:17744400916
VL - 74
SP - 487
EP - 493
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 2
ER -