Peripheral tachykinins and the NK1 receptor regulate platelet function

Tachykinins are a family of neuropeptides characterised by the conserved C-terminal motif FXGLM-NH2, where X represents a hydrophobic amino acid. Substance P (SP) a member of the tachykinin family has recently been shown to stimulate platelet aggregation and a SP-like immunoreactivity has been demonstrated in platelets and shown to be released upon platelet activation, suggesting that SP may act as a secondary platelet agonist. In recent years a gene encoding new members of the tachykinin family has been identified named TTAC4, which unlike the classical tachykinins is predominantly expressed in the periphery, with high expression in the megakaryocytic cell line HEL. The predicted products of the human TAC4 gene, endokinins A and B share high homology with SP and display similar binding characteristics as SP for the neurokinin-1 (NKl) receptor, which is present on the platelet surface. The high sequence homology between endokinins A and B and SP renders them indistinguishable using SP-imunoassays raising the possibility that platelets may be a source of endokinins. The purpose of this study was to assess the roles of peripheral tachykinins in regulating platelet function.EThOS - Electronic Theses Online ServiceGBUnited Kingdo