%0 Journal Article
%T The vasoconstrictor activities of prostaglandin D2 via the thromboxane prostanoid receptor and E prostanoid receptor-3 outweigh its concurrent vasodepressor effect mainly through D prostanoid receptor-1 ex vivo and in vivo.
%A Guo T
%A Liu B
%A Zeng R
%A Lin R
%A Guo J
%A Yu G
%A Xu Y
%A Tan X
%A Xie K
%A Zhou Y
%J Eur J Pharmacol
%V 956
%N 0
%D 2023 Oct 5
%M 37543159
%F 5.195
%R 10.1016/j.ejphar.2023.175963
%X Prostaglandin (PG) D2, a commonly considered vasodilator through D prostanoid receptor-1 (DP1), might also evoke vasoconstriction via acting on the thromboxane (Tx)-prostanoid receptor (the original receptor of TxA2; TP) and/or E prostanoid receptor-3 (one of the vasoconstrictor receptors of PGE2; EP3). This study aimed to test the above hypothesis in the mouse renal vascular bed (main renal arteries and perfused kidneys) and/or mesenteric resistance arteries and determine how the vasoconstrictor mechanism influences the overall PGD2 effect on systemic blood pressure under in vivo conditions. Experiments were performed on control wild-type (WT) mice and mice with deficiencies in TP (TP-/-) and/or EP3 (EP3-/-). Here we show that PGD2 indeed evoked vasoconstrictor responses in the above-mentioned tissues of WT mice, which were however not only reduced by TP-/- or EP3-/-, but also reversed by TP-/-/EP3-/- in some of the above tissues (mesenteric resistance arteries or perfused kidneys) to dilator reactions that were reduced by non-selective DP antagonism. A slight or mild pressor response was also observed with PGD2 under in vivo conditions, and this was again reversed to a depressor response in TP-/- or TP-/-/EP3-/- mice. Non-selective DP antagonism reduced the PGD2-evoked depressor response in TP-/-/EP3-/- mice as well. These results thus demonstrate that like other PGs, PGD2 activates TP and/or EP3 to evoke vasoconstrictor activities, which can outweigh its concurrent vasodepressor activity mediated mainly through DP1, and hence result in a pressor response, although the response might only be of a slight or mild extent.