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Inhibitory effects of ω‐3 polyunsaturated fatty acids on receptor‐mediated non‐selective cation currents in rat A7r5 vascular smooth muscle cells
Author(s) -
Asano Michiko,
Nakajima Toshiaki,
Iwasawa Kuniaki,
Hazama Hisanori,
Omata Masao,
Soma Masaaki,
Yamashita Kamejiro,
Okuda Yukichi
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701047
Subject(s) - polyunsaturated fatty acid , docosahexaenoic acid , agonist , chemistry , eicosapentaenoic acid , docosapentaenoic acid , arachidonic acid , vascular smooth muscle , biophysics , inhibitory postsynaptic potential , medicine , reversal potential , patch clamp , endocrinology , biochemistry , receptor , fatty acid , biology , smooth muscle , enzyme
The effects of ω‐3 polyunsaturated fatty acids on receptor‐mediated non‐selective cation current ( I cat ) and K + current were investigated in aortic smooth muscle cells from foetal rat aorta (A7r5 cells). The whole‐cell voltage clamp technique was employed. With a K + ‐containing solution, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, 30 μ m ) produced an outward current at a holding potential of −40 mV. This response was inhibited by tetraethylammonium (20 m m ) or Cs + in the patch pipette solution, and the reversal potential of the EPA‐induced current followed the K + equilibrium potential in a near Nernstian manner. Under conditions with a Cs + ‐containing pipette solution, both vasopressin and endothelin‐1 (100 n m ) induced a long‐lasting inward current at a holding potential of −60 mV. The reversal potential of these agonist‐induced currents was about +0 mV, and was not significantly altered by the replacement of the extracellular or intracellular Cl − concentration, suggesting that the induced current was a cation‐selective current ( I cat ). La 3+ and Cd 2+ (1 m m ) completely abolished these agonist‐induced I cat , but nifedipine (10 μ m ) failed to inhibit it significantly. ω‐3 polyunsaturated fatty acids (3100 μ m ), EPA, DHA and docosapentaenoic acids (DPA), inhibited the agonist‐induced I cat in a concentration‐dependent manner. The potency of the inhibitory effect was EPA>DHA>DPA, and the half maximal inhibitory concentration (IC 50 ) of EPA was about 7 μ m . Arachidonic and linoleic acids (10, 30 μ m ) showed a smaller inhibitory effect compared to ω‐3 fatty acids. Also, oleic and stearic acids (30 μ m ) did not show a significant inhibitory effect on I cat . A similar inhibitory action of EPA was observed when I cat was activated by intracellularly applied GTPγS in the absence of agonists, suggesting that the site of action of ω‐3 fatty acids is not located on the receptor. These results demonstrate that ω‐3 polyunsaturated fatty acids can activate a K + current and also effectively inhibit receptor‐mediated non‐selective cation currents in rat A7r5 vascular smooth muscle cells. Thus, the data suggest that ω‐3 fatty acids may play an important role in the regulation of vascular tone.British Journal of Pharmacology (1997) 120 , 1367–1375; doi: 10.1038/sj.bjp.0701047