title: Properties of Rikkunshi-to (TJ-43)-induced relaxation of rat gastric fundus smooth muscles.
abstract: The relaxant effects of Rikkunshi-to (TJ-43), a gastroprotective herbal medicine, on rat gastric fundus were investigated. Experiments were carried out using standard tension and intracellular microelectrode recording techniques. During contraction induced by enprostil (0.5 microM), a prostaglandin E(2) analog, TJ-43, produced relaxation dose dependently (0.1-5.0 mg/ml) in the rat fundic circular smooth muscle (CSM) strips. The relaxant effects of TJ-43 were not affected by tetrodotoxin or 1 H[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (10 microM), an inhibitor of soluble guanylate cyclase. TJ-43 inhibited enprostil-induced membrane depolarization. Apamin (1 microM), a blocker of small-conductance Ca(2+)-activated K(+) (SK) channel, inhibited T-43-induced membrane repolarization. TJ-43-induced relaxation was biphasic, comprising of an initial fast followed by a second slow relaxation. The fast relaxation was abolished by apamin. Application of high K(+) (29.4 mM [K(+)](o)) also abolished the fast relaxation induced by TJ-43. In diabetic Goto-Kakizaki (GK) rat fundic CSM strips, the relaxant responses of TJ-43 during enprostil-induced contraction were increased compared with control rat strips. These results indicate that TJ-43 elicited fast muscle relaxation through membrane hyperpolarization induced by the activation of SK channels; the time-dependent slow relaxation reflects an additional direct of TJ-43 on CSM in the rat gastric fundus. Because TJ-43-evoked relaxation of fundic CSM strips was more potent in diabetic GK rat than in control rat, further analysis of this herb could lead to better treatments of diabetic gastroparesis.
authors.affiliation: Dept. of Physiology, Nagoya City Univ. Medical School, Mizuho-ku, Nagoya, Japan. y.kito@med.nagoya-cu.ac.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kito
authors.forename: Hikaru
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D016620:Enprostil / Q000037:antagonists & inhibitors; D005748:Gastric Fundus / Q000187:drug effects*; D006569:Hesperidin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology; D011188:Potassium / Q000008:administration & dosage; D011744:Pyrimidinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004365:Drugs, Chinese Herbal; D010069:Oxadiazoles; D011744:Pyrimidinones; D011810:Quinoxalines; D013844:Thiazoles; C084136:liu-jun-zi-tang; D001030:Apamin; C047505:R 59022; D014700:Verapamil; D006569:Hesperidin; D016620:Enprostil; D011188:Potassium