Article date: March 1997
By: Michiko Asano, Toshiaki Nakajima, Kuniaki Iwasawa, Hisanori Hazama, Masao Omata, Masaaki Soma, Kamejiro Yamashita, Yukichi Okuda, in Volume 120, Issue 7, pages 1367-1375
The effects of ω‐3 polyunsaturated fatty acids on receptor‐mediated non‐selective cation current (Icat) 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 μm) produced an outward current at a holding potential of −40 mV. This response was inhibited by tetraethylammonium (20 mm) 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 nm) 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 (Icat).
La3+ and Cd2+ (1 mm) completely abolished these agonist‐induced Icat, but nifedipine (10 μm) failed to inhibit it significantly.
ω‐3 polyunsaturated fatty acids (3100 μm), EPA, DHA and docosapentaenoic acids (DPA), inhibited the agonist‐induced Icat in a concentration‐dependent manner. The potency of the inhibitory effect was EPA>DHA>DPA, and the half maximal inhibitory concentration (IC50) of EPA was about 7 μm.
Arachidonic and linoleic acids (10, 30 μm) showed a smaller inhibitory effect compared to ω‐3 fatty acids. Also, oleic and stearic acids (30 μm) did not show a significant inhibitory effect on Icat.
A similar inhibitory action of EPA was observed when Icat 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.
The effects of ω‐3 polyunsaturated fatty acids on receptor‐mediated non‐selective cation current (Icat) 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 μm) produced an outward current at a holding potential of −40 mV. This response was inhibited by tetraethylammonium (20 mm) 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 nm) 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 (Icat).
La3+ and Cd2+ (1 mm) completely abolished these agonist‐induced Icat, but nifedipine (10 μm) failed to inhibit it significantly.
ω‐3 polyunsaturated fatty acids (3100 μm), EPA, DHA and docosapentaenoic acids (DPA), inhibited the agonist‐induced Icat in a concentration‐dependent manner. The potency of the inhibitory effect was EPA>DHA>DPA, and the half maximal inhibitory concentration (IC50) of EPA was about 7 μm.
Arachidonic and linoleic acids (10, 30 μm) showed a smaller inhibitory effect compared to ω‐3 fatty acids. Also, oleic and stearic acids (30 μm) did not show a significant inhibitory effect on Icat.
A similar inhibitory action of EPA was observed when Icat 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
DOI: 10.1038/sj.bjp.0701047
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