title: Nitrergic Pathway Is the Major Mechanism for the Effect of DA-9701 on the Rat Gastric Fundus Relaxation.
abstract: OBJECTIVE
  DA-9701 significantly improved gastric accommodation by increasing the postprandial gastric volume. In this study, we investigated how DA-9701 affects the rat gastric fundus relaxation.
  
  
  METHODS
  Gastric fundus muscle strips (9 longitudinal and 7 circular muscles) were obtained from rats. Electrical field stimulation (EFS) was performed at various frequencies (1, 5, 10 and 20 Hz) and train durations (1, 5, 10 and 20 seconds) to select optimal condition for experiments. Isometric force measurements were performed in response to EFS. Peak and nadir were observed during the first 1 minute after initiation of EFS in control state and after sequential addition of atropine (1 μM), DA-9701 (0.5, 5, 25 and 50 μg), N-nitro-L-arginine (L-NNA, 100 μM), MRS2500 (1 μM) and tetrodotoxin (TTX, 1 μM) to the organ bath.
  
  
  RESULTS
  The optimal frequency and duration of EFS to evoke nerve-mediated relaxation was determined as 5 Hz for 10 seconds. Addition of L-NNA in the presence of atropine and DA-9701 (50 μg) decreased nadir by inhibiting relaxation from -0.054 ± 0.021 g to -0.022 ± 0.015 g (P = 0.026) in longitudinal muscles. However, subsequent application of MRS2500 in the presence of atropine, DA-9701 (50 μg) and L-NNA did not affect nadir. In circular muscles, subsequent addition of L-NNA and MRS2500 in the presence of atropine and DA-9701 (50 μg) did not show significant change of nadir.
  
  
  CONCLUSIONS
  Our data suggest that the effect of DA-9701 on the rat gastric fundus relaxation is mainly mediated by nitrergic rather than purinergic pathway.
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yang Won
authors.initials: YW
authors.lastname: Min
authors.affiliation: Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Ko
authors.affiliation: Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Min
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jun Haeng
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Poong-Lyul
authors.initials: PL
authors.lastname: Rhee
keywords: DA-9701, Gastric fundus, Rats, Relaxation