Effect of SC-435 on the gastrointestinal migrating myoelectric complex in guinea pigs.
OBJECTIVE
To determine whether SC-435, a new ileal apical sodium-codependent bile acid transporter (IBAT) inhibitor, can alter the gastrointestinal motility in guinea pigs.


METHODS
Sixty guinea pigs received regular diet or IBAT inhibitor (SC-435) diet for 2, 4, and 8 weeks, respectively. At the end of the feeding period, the gallbladder motility was assessed and then four bipolar silver electrodes were implanted on the antrum, duodenum, jejunum, and ileum. Seven days later, migrating motor complex (MMC) was recorded and the total bile acid pool size was measured according to the isotope dilution principle in the meantime.


RESULTS
After feeding SC435, the gallbladder motility was declined in the 4-week group and the 8-week group. The bile acid pool size decreased by 17.11% (P <0.05) in the 4-week group and 48.35% (P < 0.05) in the 8-week group. The places of origin of MMC were changed where antral origins (37%) and duodenal origins (46%) decreased whereas jejunal origins (17%) increased. The MMC cycle period was prolonged in the duodenum (1.16 times in the 4-week group, P < 0.05; 1.38 times in the 8-week group, P < 0.05) whereas MMC amplitude fell in the duodenum (10.58% in the 4-week group, P <0.05; 49.17% in the 8-week group, P <0.05). There were not significant differences in all parameters of MMC between the control group and the 2-week group in guinea pigs.


CONCLUSIONS
The IBAT inhibitor (SC-435) reduces the bile acid pool size and inhibits the MMC cycle activity. MMC is related to the enterohepatic circulation of bile acids, which is consistent with the changes of the bile acid pool size in guinea pigs.
Zhang
Xue-mei
XM
Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Dong
Lei
L
Liu
Li-na
LN
Lei
Ya-mei
YM
D000818:Animals; D001647:Bile Acids and Salts; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005260:Female; D005704:Gallbladder / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D016065:Myoelectric Complex, Migrating / Q000187:drug effects*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D027981:Symporters / Q000037:antagonists & inhibitors*; D014326:Tropanes / Q000494:pharmacology*
C466800:1-(4-(4-(3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl)phenoxy)butyl)-4-aza-1-azoniabicyclo(2.2.2)octane; D001647:Bile Acids and Salts; D003497:Cyclic N-Oxides; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; D014326:Tropanes; C071908:sodium-bile acid cotransporter