Enprostil

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 μM), a prostaglandin E2 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 μM), an inhibitor of soluble guanylate cyclase. TJ-43 inhibited enprostil-induced membrane depolarization. Apamin (1 μM), a blocker of small-conductance Ca2+-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.

A study group supported by Ministry of Health, Labor and Welfare recently reported the Japanese guideline for gastric ulcer treatment which suggests that gastric ulcer can be cured by either H. pylori eradication or acid suppression therapy by proton pump inhibitors(PPI) and H2-receptor antagonists(H2RA). It also suggests that all mucoprotective drugs except sucrafate, misoprostol and enprostil can't be recommended for gastric ulcer treatment. However, some mucoprotective drugs have been shown to possess anti-inflammatory action, leading to the inhibition of leucocyte infiltration in H. pylori gastritis, while long-term usage of PPI and H2RA might worsen gastritis. Thus, mucoprotective drugs should be investigated in terms of long-term effects on H. pylori-gastritis rather than the effects on gastric ulceration.