C 2-ceramide attenuates prostaglandin F 2 α-induced vasoconstriction and elevation of [Ca 2+] i in canine cerebral vascular smooth muscle

Abstract

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 C 2-ceramide, a cell-permeable sphingolipid, on contraction of canine cerebral vascular smooth muscle and intracellular free Ca 2+ ([Ca 2+] i). C 2-ceramide (10 −8–10 −4 M) alone did not elicit any significant changes in either basal tension or resting levels of [Ca 2+] i in canine cerebrovascular muscle. However, C 2-ceramide (10 −7–10 −4 M) attenuated prostaglandin F 2 α (PGF 2 α )-induced contractions in isolated canine cerebrovascular smooth muscle rings. C 2-ceramide (10 −5 M) inhibited the secondary phasic rise of [Ca 2+] i evoked by PGF 2 α in cultured canine cerebral vascular smooth muscle cells, resulting in decreases in the elevation in [Ca 2+] 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 C 2-ceramide. Our results suggest that the sphingomyelin signaling pathway may play an important regulatory role in cerebral arterial wall tone.