The Effect of Phosphodiesterase Type 4 and 5 Inhibitors on Ileal Motor Function of the Guinea Pig

Park, Hyo Jin; Choi, Sung Woo; Lee, Yong Ho; Lim, Jung Hyun; Lee, Sang In; Park, In Suh

Abstract

BACKGROUND/AIMS: Intracellular cAMP or cGMP is degraded by cyclic nucleotide phosphodiesterase (PDE). We hypothesized that PDE inhibitors modulate the peristalsis and nerve-induced responses of the smooth muscle of the guinea pig ileum.
METHODS
To examine the effect of rolipram (type 4 inhibitor of PDE) and zaprinast (type 5 inhibitor of PDE), we measured peristaltic amplitude, area under curve (AUC), and frequency of contractions from ileal preparation using the peristaltic bath. The mechanical activity of the circular muscle was measured with a clip attached, via the three sites of serosal surface, to the underlying circular muscle of intact ileum in the peristaltic chamber. In another set of experiment, muscle strips from the ileum were stimulated by an electrical field. The effects of rolipram, and zaprinast, on peristalsis and nerve-induced contraction were explored.
RESULTS
The amplitude and AUC of peristaltic contractions were significantly decreased in rolipram or zaprinast-treated group and frequency of contractions was significantly delayed in rolipram or zaprinast-treated group. The nerve-induced contraction of smooth muscle was significantly decreased in rolipram-treated group.
CONCLUSIONS
These observations suggest that PDEs may play a role in the modulation of peristaltic behavior of the ileum and PDE inhibitors may be used in the treatment of hyperkinetic bowel disorders.