Differential properties of E prostanoid receptor-3 and thromboxane prostanoid receptor in activation by prostacyclin to evoke vasoconstrictor response in the mouse renal vasculature.

Bin Liu, Ruhui Zeng, Tingting Guo, Yingzhan Zhang, Jing Leng, Jiahui Ge, Gang Yu, Yineng Xu, Yingbi Zhou

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2020 Dec

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Vasomotor reactions of prostacyclin (prostaglandin I2 ; PGI2 ) can be collectively modulated by thromboxane prostanoid receptor (TP), E-prostanoid receptor-3 (EP3), and the vasodilator I prostanoid receptor (IP). This study aimed to determine the direct effect of PGI2 on renal arteries and/or the whole renal vasculature and how each of these receptors is involved. Experiments were performed on vessels or perfused kidneys of wild-type mice and/or mice with deficiency in TP (TP-/- ) and/or EP3. Here we show that PGI2 did not evoke relaxation, but instead resulted in contraction of main renal arteries (from ~0.001-0.01 µM) or reduction of flow in perfused kidneys (from ~1 µM); either of them was reversed into a dilator response in TP-/- /EP3-/- counterparts. Also, we found that in renal arteries although it has a lesser effect than TP-/- on the maximal contraction to PGI2 (10 µM), EP3-/- but not TP-/- resulted in relaxation to the prostanoid at 0.01-1 µM. Meanwhile, TP-/- only significantly reduced the contractile activity evoked by PGI2 at ≥0.1 µM. These results demonstrate that PGI2 may evoke an overall vasoconstrictor response in the mouse renal vasculature, reflecting activities of TP and EP3 outweighing that of the vasodilator IP. Also, our results suggest that EP3, on which PGI2 can have a potency similar to that on IP, plays a major role in the vasoconstrictor effect of the prostanoid of low concentrations (≤1 µM), while TP, on which PGI2 has a lower potency but higher efficacy, accounts for a larger part of its maximal contractile activity. © 2020 Federation of American Societies for Experimental Biology.

Citation

Bin Liu, Ruhui Zeng, Tingting Guo, Yingzhan Zhang, Jing Leng, Jiahui Ge, Gang Yu, Yineng Xu, Yingbi Zhou. Differential properties of E prostanoid receptor-3 and thromboxane prostanoid receptor in activation by prostacyclin to evoke vasoconstrictor response in the mouse renal vasculature. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020 Dec;34(12):16105-16116