Effect of ceramide on the contractility of pregnant rat uterus.

Ceramide and other sphingolipid mediators have emerged as a novel class of lipid second messengers in cell signaling. We assessed the effect of C(2)-ceramide (a membrane permeable analog of ceramide) on spontaneous and agonist-induced contractile responses of uterus, isolated from 19-day pregnant rats. Ceramide (3, 10 microM) moderately, but significantly inhibited the amplitude of spontaneous rhythmic contractions. However, a variable effect was seen on agonist-induced contractions. While 5-HT-induced contractions were markedly inhibited at 3 and 10 microM ceramide, oxytocin and carboprost (a PGF(2)alpha analogue)-induced contractions were not affected by the sphingolipid. Ceramide (10 microM) also markedly inhibited CaCl(2)-induced contractions elicited in K(+)-depolarized tissues. Further, in rabbit portal vein myocytes, which display robust L-type calcium channel current, ceramide inhibited the I(Ba) in a dose-dependent manner. Therefore, it is suggested that the inhibitory effect of ceramide on uterine contractility may involve a decrease in the influx of Ca(2+) through voltage-dependent L-type Ca(2+) channels, such that contractile responses that are primarily dependent on extracellular Ca(2+), like rhythmic and serotonin contractions, were inhibited by ceramide. Further study is required to establish the role of endogenous ceramide and other sphingolipids in regulating uterine tone during gestation and at term.