C2-ceramide attenuates prostaglandin F2alpha-induced vasoconstriction and elevation of (Ca2+)i in canine cerebral vascular smooth muscle.

摘要

Sphingolipids have emerged as important components of signal transduction pathways involved in a variety of cellular processes. In the present study, we examined the effects of C2-ceramide, a cell-permeable sphingolipid, on contraction of canine cerebral vascular smooth muscle and intracellular free Ca2+ ([Ca2+]i). C2-ceramide (10(-8)-10(-4) M) alone did not elicit any significant changes in either basal tension or resting levels of [Ca2+]i in canine cerebrovascular muscle. However, C2-ceramide (10(-7)-10(-4) M) attenuated prostaglandin F2alpha (PGF2alpha)-induced contractions in isolated canine cerebrovascular smooth muscle rings. C2-ceramide (10(-5) M) inhibited the secondary phasic rise of [Ca2+]i evoked by PGF2alpha in cultured canine cerebral vascular smooth muscle cells, resulting in decreases in the elevation in [Ca2+]i. NO inhibitors (L-NNA, L-NMMA), an inhibitor of prostanoid synthesis (indomethacin), an inhibitor of opiate actions and several inhibitors of the pharmacologic actions of various vasoactive amines all failed to interfere with the vasorelaxant response of C2-ceramide. Our results suggest that the sphingomyelin signaling pathway may play an important regulatory role in cerebral arterial wall tone.