Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells.
Stimulation of vascular smooth muscle (VSM) α1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. Δ6 (D6d) and Δ5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2α secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction.
Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
Nicola A
NA
Irvine
Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK.
Karen A
KA
Lillycrop
Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
Barbara
B
Fielding
Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
Christopher
C
Torrens
Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
Mark A
MA
Hanson
Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. Electronic address: g.c.burdge@soton.ac.uk.
Graham C
GC
Burdge
D000123:Acetyltransferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D015777:Eicosanoids / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000187:drug effects / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010656:Phenylephrine / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D044943:Fatty Acid Desaturases; D000123:Acetyltransferases; D002118:Calcium
Calcium; Polyunsaturated fatty acids; Vascular smooth muscle cells