Expression and functional evidence of the prostaglandin F2α receptor mediating contraction in human umbilical vein

被引:10
作者
Emilse Errasti, Andrea [1 ,2 ]
del-Rey, Gianina [1 ]
Emanuel Cesio, Cristian [1 ]
Souza, Guadalupe [1 ]
Nowak, Wanda [1 ]
German Pelorosso, Facundo [1 ]
Manuel Daray, Federico [1 ]
Pedro Rothlin, Rodolfo [1 ]
机构
[1] Univ Buenos Aires, Fac Med, Dept Farmacol, RA-1121 Buenos Aires, DF, Argentina
[2] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina
关键词
Human umbilical vein; Vasoconstriction; Prostaglandin F-2 alpha (PGF(2 alpha)); Latanoprost free acid; Bimatoprost free acid; AL-8810; RT-PCR (Reverse transcription-polymerase chain reaction); Western blot; PGF(2 alpha) receptor (prostanoid FP-receptor); INTRACELLULAR CA2+ MOBILIZATION; LIGHT-CHAIN PHOSPHORYLATION; IN-VITRO CHARACTERIZATION; SMOOTH-MUSCLE; PROSTANOID RECEPTORS; FP RECEPTOR; HUMAN MYOMETRIUM; ENDOTHELIAL-CELLS; IRIS SPHINCTER; MESSENGER-RNA;
D O I
10.1016/j.ejphar.2009.03.022
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Our purposes were to perform the pharmacological characterization of PGF(2 alpha) receptor (prostanoid FP-receptor) involved in human umbilical vein contraction and confirm its expression in this tissue. Umbilical cords from healthy patients after full-term deliveries were employed. The vein was dissected out of cords and used for either isolated organ bath or reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays. The natural prostanoid FP-receptor agonist, PGF(2 alpha), and its selective analogues, latanoprost and bimatoprost free acids are full agonists (produce more than 80% of the maximal contractile response to 5-HT) in human umbilical vein. The agonist potency (pEC(50)) order was PGF(2 alpha) (6.01 +/- 0.05)>latanoprost free acid (5.65 +/- 0.07) = bimatoprost free acid (5.59 +/- 0.08). The contractile effects of PGF(2 alpha) and latanoprost free acid were blocked competitively by the prostanoid FP-receptor antagonist, AL-8810. The antagonist potencies (pK(B)) of AL-8810 vs. PGF(2 alpha) (5.93 +/- 0.05) and vs. latanoprost free acid (6.40 +/- 0.08) in human umbilical vein are in good agreement with its ability to antagonize prostanoid FP receptors of rat, mouse and human cells. In all samples, clear signal was detected for cDNA amplification of prostanoid FP receptor and the specific prostanoid FP-receptor antibody recognized a protein of approximately 64 kDa. In conclusion, taking into account the obtained functional and biochemical data, we propose for the first time that human umbilical vein express prostanoid FP-receptors and these receptors could be involved in the vasoconstriction action of PGF(2 alpha) in this tissue. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:68 / 74
页数:7
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