Expression and functional evidence of the prostaglandin F(2alpha) receptor

ERRASTI AE, DEL-REY G, CESIO CE, SOUZA G, NOWAK W, PELOROSSO FG, DARAY FM,

EUROPEAN JOURNAL OF PHARMACOLOGY

Elsevier Science

Lugar: Netherlands; Año: 2009 vol. 610 p. 68 - 74

0014-2999

Received 25 September 2008;  revised 16 February 2009;  accepted 3 March 2009.  Available online 14 March 2009. Abstract Our purposes were to perform the pharmacological characterization of PGF2á 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, PGF2á, 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 (pEC50) order was PGF2á (6.01 ± 0.05) > latanoprost free acid (5.65 ± 0.07) = bimatoprost free acid (5.59 ± 0.08). The contractile effects of PGF2á and latanoprost free acid were blocked competitively by the prostanoid FP-receptor antagonist, AL-8810. The antagonist potencies (pKB) of AL-8810 vs. PGF2á (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 PGF2á in this tissue. Keywords: Human umbilical vein; Vasoconstriction; Prostaglandin F2á (PGF2á); Latanoprost free acid; Bimatoprost free acid; AL-8810; RT-PCR (Reverse transcription-polymerase chain reaction); Western blot; PGF2á receptor (prostanoid FP-receptor)