Sphingolipids such as sphingosine‐1‐phosphate (SPP) and sphingosylphosphorylcholine (SPPC) can act both intracellularly and at G‐protein‐coupled receptors, some of which were cloned and designated as Edg‐receptors.

Sphingolipid‐induced vascular effects were determined in isolated rat mesenteric and intrarenal microvessels. Additionally, sphingolipid‐induced elevations in intracellular Ca²⁺ concentration were measured in cultured rat aortic smooth muscle cells.

SPPC and SPP (0.1–100 μmol l⁻¹) caused concentration‐dependent contraction of mesenteric and intrarenal microvessels (e.g. SPPC in mesenteric microvessels pEC₅₀ 5.63±0.17 and E_max 49±3% of noradrenaline), with other sphingolipids being less active. The vasoconstrictor effect of SPPC in mesenteric microvessels was stereospecific (pEC₅₀ D‐erythro‐SPPC 5.69±0.08, L‐threo‐SPPC 5.31±0.06) and inhibited by pretreatment with pertussis toxin (E_max from 44±5 to 19±4%), by chelation of extracellular Ca²⁺ with EGTA and by nitrendipine (E_max from 40±6 to 6±1 and 29±6%, respectively). Mechanical endothelial denudation or NO synthase inhibition did not alter the SPPC effects, while indomethacin reduced them (E_max from 87±3 to 70±4%).

SPP and SPPC caused transient increases in intracellular Ca²⁺ concentrations in rat aortic smooth muscle cells in a pertussis toxin‐sensitive manner.

Our data demonstrate that SPP and SPPC cause vasoconstriction of isolated rat microvessels and increase intracellular Ca²⁺ concentrations in cultured rat aortic smooth muscle cells. These effects appear to occur via receptors coupled to pertussis toxin‐sensitive G‐proteins. This is the first demonstration of effects of SPP and SPPC on vascular tone and suggests that sphingolipids may be an hitherto unrecognized class of endogenous regulators of vascular tone.