Roles of endogenous prostaglandins and nitric oxide in inhibitions of gastric emptying and accelerations of gastrointestinal transit by escins Ia, Ib, IIa, and IIb in mice.
We reported previously that escins Ia, Ib, IIa, and IIb, isolated from horse chestnuts, inhibited the 30-min gastric emptying (GE) in mice. In this study, the effects of escins Ia-IIb on gastrointestinal transit (GIT), and the roles of endogenous prostaglandins (PGs) and nitric oxide (NO) in the effects of escins Ia--IIb on GE and GIT were investigated in fasted mice. Escins Ia-IIb (12.5-50 mg/kg, p.o.) dose-dependently accelerated GIT. Both GE inhibitions and GIT accelerations by escins Ia-IIb (25 mg/kg) were markedly attenuated by pretreatment with indomethacin (10 mg/kg, s.c., an inhibitor of PGs synthesis). Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p., an inhibitor of constitutive and inducible NO synthase) attenuated the effects of escins Ia-IIb on GIT, but not on GE. The effect of L-NAME was reversed by L-arginine (600 mg/kg, i.p., a substrate of NO synthase), but not by D-arginine (900 mg/kg, i.p., the enantiomer of L-arginine). The GIT accelerations of escins Ia-IIb were not attenuated by pretreatment with D-NAME (10 mg/kg, i.p., the enantiomer of L-NAME) or dexamethasone (5 mg/kg, i.p., an inhibitor of inducible form of NO synthase). The results suggest that endogenous PGs play an important role in both GE inhibitions and GIT accelerations, and constitutive NO is involved in the GIT accelerations, by escins Ia--IIb in mice.
Matsuda
H
H
Kyoto Pharmaceutical University, Japan.
Li
Y
Y
Yoshikawa
M
M
D000818:Animals; D004928:Escin / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*
D011453:Prostaglandins; D009569:Nitric Oxide; D004928:Escin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin