Relaxation effect of synthetic ceramide analogues in cat esophageal smooth muscle cells.
Ceramide has emerged as a novel second messenger for intracellular signalling. It is produced from sphingomyelin and is involved in the control of cell differntiation, proliferation, and apoptosis. C(2)-ceramide, short chain ceramide, plays a role in mediating contraction of cat esophageal smooth muscle cells. We examined the effect of synthesized ceramide analogues on the C(2)-ceramide and ACh-induced contraction in esophageal smooth muscle cells isolated with collagenase. CY3523, CY3525, or CY3723 inhibited C(2)-ceramide induced contraction, in a time dependent manne. Each analogue also inhibited the contraction in concentration dependent manners. CY 3523, CY 3525, and CY 3723 had no effect to the contraction induced by PMA. The inhibition with CY3523, CY3525 and CY3723 on the C(2)-ceramide induced contraction was recovered by PMA. These analogues decreased the density of MAPK bands (p44/42 or p38) in the western blot. These results suggest that ceramide analogues can inhibit C(2)-ceramide induced contraction via PKC and MAPK dependent pathway.
Lee
Doo Won
DW
College of Pharmacy, Chung Ang University, Seoul, Korea.
Park
Sun Young
SY
Ryu
Jung Su
JS
Kim
Sung Hyo
SH
Im
Chae Uk
CU
Choi
Su Hang
SH
Lee
Se Eun
SE
Ko
Sung Kwon
SK
Sohn
Uy Dong
UD