Contractile Actions of Thrombin Receptor-derived Polypeptides in Human Umbilical and Placental Vasculature: Evidence for Distinct Receptor Systems

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1995 Jun 1

PMID 7582474

Citations 6

Authors

M C Poon

S Ahmad

M D Hollenberg

Affiliations

Soon will be listed here.

Abstract

1. We studied the structure-activity profiles of four thrombin receptor-derived polypeptides (TRPs) (P5, SFLLR; P5-NH2, SFLLR-NH2; P7, SFLLRNP; P7-NH2, SFLLRN) in contractile human placental artery (PA), umbilical artery (UA) and umbilical vein (UV) preparations and in a human platelet aggregation assay. 2. The contractile actions of the TRPs in the two arterial preparations were endothelium-independent, whereas in the UV tissue a contractile response was observed only in an endothelium-denuded preparation; no endothelium-mediated relaxation responses were observed in any of the vascular preparations. 3. In the three vascular preparations, the contractile responses required extracellular calcium and were attenuated by the tyrosine kinase inhibitor, genistein. 4. The relative contractile orders of potencies of the TRPs in the three vascular preparations were distinct from each other (PA: P7-NH2 > P7 > P5-NH2 > P5; UA: P7-NH2 > or = P5-NH2 approximately = P7 > > P5; UV: P5-NH2 > > P7-NH2 = P7 > > P5) and these were in turn distinct from the potency order observed in the platelet aggregation assay (P5-NH2 > or = P7-NH2 > P7 > > P5). 5. Despite the markedly dissimilar TRP potency orders in the placental artery and umbilical vein preparations, the cDNA sequences for the thrombin receptor obtained by polymerase chain reaction cloning of cDNA from the two tissue sources were identical. 6. We conclude that the four tissues studied possess functionally distinct thrombin receptor systems that interact in a distinct way with agonist peptides. In view of the identity of the thrombin receptor cDNA in the two tissues displaying the most dissimilar structure-activity profiles, we suggest that in different tissues, differences in post-translational receptor processing or differences in receptor-effector coupling interactions may result in unique thrombin receptor systems that can display distinct structure-activity profiles.

Citing Articles

Pharmacological effects of recombinant human tissue kallikrein on bradykinin B2 receptors.

Charest-Morin X, Raghavan A, L Charles M, Kolodka T, Bouthillier J, Jean M Pharmacol Res Perspect. 2015; 3(2):e00119.

PMID: 26038695 PMC: 4448978. DOI: 10.1002/prp2.119.

Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro.

Tognetto M, DAndrea M, Trevisani M, Guerrini R, Salvadori S, Spisani L Br J Pharmacol. 2003; 139(1):21-7.

PMID: 12746219 PMC: 1573818. DOI: 10.1038/sj.bjp.0705215.

Contractile actions of proteinase-activated receptor-derived polypeptides in guinea-pig gastric and lung parenchymal strips: evidence for distinct receptor systems.

Saifeddine M, Sandhu S, Wijesuriya S, Hollenberg M Br J Pharmacol. 2001; 132(2):556-66.

PMID: 11159706 PMC: 1572581. DOI: 10.1038/sj.bjp.0703839.

Enhanced contractile response to thrombin in the pregnant rat myometrium.

Shintani Y, Hirano K, Nishimura J, Nakano H, Kanaide H Br J Pharmacol. 2001; 131(8):1619-28.

PMID: 11139439 PMC: 1572489. DOI: 10.1038/sj.bjp.0703729.

Pro- and anti-inflammatory actions of thrombin: a distinct role for proteinase-activated receptor-1 (PAR1).

Vergnolle N, Hollenberg M, Wallace J Br J Pharmacol. 1999; 126(5):1262-8.

PMID: 10205017 PMC: 1565884. DOI: 10.1038/sj.bjp.0702408.

References

Davey M, LUSCHER E . Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets. Nature. 1967; 216(5118):857-8. DOI: 10.1038/216857a0. View

Nystedt S, Emilsson K, Wahlestedt C, Sundelin J . Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci U S A. 1994; 91(20):9208-12. PMC: 44781. DOI: 10.1073/pnas.91.20.9208. View

White R, Chapleau C, Dugdale M, Robertson J . Cerebral arterial contractions induced by human and bovine thrombin. Stroke. 1980; 11(4):363-8. DOI: 10.1161/01.str.11.4.363. View

De Mey J, Claeys M, Vanhoutte P . Endothelium-dependent inhibitory effects of acetylcholine, adenosine triphosphate, thrombin and arachidonic acid in the canine femoral artery. J Pharmacol Exp Ther. 1982; 222(1):166-73. View

White R, Shirasawa Y, Robertson J . Comparison of responses elicited by alpha-thrombin in isolated canine basilar, coronary, mesenteric, and renal arteries. Blood Vessels. 1984; 21(1):12-22. DOI: 10.1159/000158490. View

Haver V, Namm D . Characterization of the thrombin-induced contraction of vascular smooth muscle. Blood Vessels. 1984; 21(2):53-63. View

Rapoport R, Draznin M, Murad F . Mechanisms of adenosine triphosphate-, thrombin-, and trypsin-induced relaxation of rat thoracic aorta. Circ Res. 1984; 55(4):468-79. DOI: 10.1161/01.res.55.4.468. View

Walz D, Anderson G, Ciaglowski R, Aiken M, Fenton 2nd J . Thrombin-elicited contractile responses of aortic smooth muscle. Proc Soc Exp Biol Med. 1985; 180(3):518-26. DOI: 10.3181/00379727-180-42211. View

Walz D, Anderson G, Fenton 2nd J . Responses of aortic smooth muscle to thrombin and thrombin analogues. Ann N Y Acad Sci. 1986; 485:323-34. DOI: 10.1111/j.1749-6632.1986.tb34594.x. View

10.

Van de Voorde J, Vanderstichele H, LEUSEN I . Release of endothelium-derived relaxing factor from human umbilical vessels. Circ Res. 1987; 60(4):517-22. DOI: 10.1161/01.res.60.4.517. View

11.

Kenakin T, Morgan P . Theoretical effects of single and multiple transducer receptor coupling proteins on estimates of the relative potency of agonists. Mol Pharmacol. 1989; 35(2):214-22. View

12.

Vu T, Hung D, Wheaton V, Coughlin S . Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991; 64(6):1057-68. DOI: 10.1016/0092-8674(91)90261-v. View

13.

Chaudhuri G, Buga G, GOLD M, Wood K, Ignarro L . Characterization and actions of human umbilical endothelium derived relaxing factor. Br J Pharmacol. 1991; 102(2):331-6. PMC: 1918038. DOI: 10.1111/j.1476-5381.1991.tb12174.x. View

14.

Rasmussen U, Vouret-Craviari V, Jallat S, Schlesinger Y, Pages G, Pavirani A . cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett. 1991; 288(1-2):123-8. DOI: 10.1016/0014-5793(91)81017-3. View

15.

Coughlin S, Vu T, Hung D, Wheaton V . Characterization of a functional thrombin receptor. Issues and opportunities. J Clin Invest. 1992; 89(2):351-5. PMC: 442859. DOI: 10.1172/JCI115592. View

16.

Vassallo Jr R, Kieber-Emmons T, Cichowski K, Brass L . Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides. J Biol Chem. 1992; 267(9):6081-5. View

17.

Hui K, Jakubowski J, Wyss V, Angleton E . Minimal sequence requirement of thrombin receptor agonist peptide. Biochem Biophys Res Commun. 1992; 184(2):790-6. DOI: 10.1016/0006-291x(92)90659-9. View

18.

Chao B, Kalkunte S, Maraganore J, Stone S . Essential groups in synthetic agonist peptides for activation of the platelet thrombin receptor. Biochemistry. 1992; 31(27):6175-8. DOI: 10.1021/bi00142a001. View

19.

DeBlois D, Drapeau G, Petitclerc E, MARCEAU F . Synergism between the contractile effect of epidermal growth factor and that of des-Arg9-bradykinin or of alpha-thrombin in rabbit aortic rings. Br J Pharmacol. 1992; 105(4):959-67. PMC: 1908711. DOI: 10.1111/j.1476-5381.1992.tb09085.x. View

20.

Zhong C, Hayzer D, Corson M, Runge M . Molecular cloning of the rat vascular smooth muscle thrombin receptor. Evidence for in vitro regulation by basic fibroblast growth factor. J Biol Chem. 1992; 267(24):16975-9. View