CONTRACTILE ACTIONS OF THROMBIN RECEPTOR-DERIVED POLYPEPTIDES IN HUMAN UMBILICAL AND PLACENTAL VASCULATURE - EVIDENCE FOR DISTINCT RECEPTOR SYSTEMS

被引：26

作者：

TAYUYBOCO, J ^{[1
]}

POON, MC ^{[1
]}

AHMAD, S ^{[1
]}

HOLLENBERG, MD ^{[1
]}

机构：

[1] UNIV CALGARY, FAC MED, DEPT MED, CALGARY, AB T2N 4N1, CANADA

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 1995年 / 115卷 / 04期

关键词：

THROMBIN RECEPTOR; UMBILICAL ARTERY; PLACENTAL ARTERY; UMBILICAL VEIN; PLATELETS;

D O I：

10.1111/j.1476-5381.1995.tb14970.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 greater than or equal to P-5-NH2 similar or equal to 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 greater than or equal to 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.

引用

页码：569 / 578

页数：10

共 39 条

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