Kazuko Satoh1,*, Kazunori Hashimoto1, Terumasa Hayakawa1, Atsushi Ishige1, Misao Kaneko2, Soichiro Ogihara2, Susumu Kurosawa2, Koji Yakabi2 and Takashi Nakamura2
1Kampo & Pharmacognosy Laboratory, R & D Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan
2The Third Department of Internal Medicine, Teikyo University, School of Medicine (Ichihara Hospital) 3426-3, Anesaki, Ichihara-shi, Chiba 299-0111, Japan
*Corresponding author. FAX: +81-298-89-2158, E-mail: satou_kazuko@mail.tsumura.co.jp
Abstract: To clarify the contractile mechanism of Dai-kenchu-to, the effects of hydroxy b-sanshool (an ingredient of Zanthoxylum fruit), Zanthoxylum fruit (a constituent herb of Dai-kenchu-to) and Dai-kenchu-to were studied in mucosa-free longitudinal muscle of guinea pig ileum. Hydroxy b-sanshool at 10-7 - 10-5 g/ml induced dose-related contractions accompanied by autonomous contraction and produced an initial contraction at a concentration of 10-4 g/ml or more. The contraction induced by hydroxy b-sanshool (10-5 g/ml) was significantly inhibited by tetrodotoxin or the capsaicin-receptor antagonist capsazepine. Although atropine or the substance P antagonist spantide tended to inhibit the contraction, a combination of atropine and spantide almost abolished the contraction by hydroxy b-sanshool. The P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid did not affect hydroxy b-sanshool-induced contraction in the presence or absence of spantide. The tonic contractions by Zanthoxylum fruit (2 ´ 10-4 g/ml) and Dai-kenchu-to (10-3 g/ml) were significantly inhibited or tended to be inhibited by atropine, spantide, tetrodotoxin or capsazepine and were remarkably suppressed by the combination of atropine and spantide. These results suggested that acetylcholine release from intrinsic cholinergic nerves and tachykinins from sensory neurons are involved in the contractions induced by hydroxy b-sanshool and that tachykinins may be involved in the atropine-resistant contraction by Dai-kenchu-to.
Keywords: Dai-kenchu-to, Zanthoxylum fruit, Hydroxy b-sanshool, Intestinal motility, Tachykinin
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