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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1058-1065.
Prepublished online as a Blood First Edition Paper on May 6, 2004; DOI 10.1182/blood-2003-11-3979.
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Submitted November 19, 2003
Accepted April 26, 2004
Tachykinins regulate the function of platelets
Gwenda J Graham, Joanne M Stevens, Nigel M Page, Andrew D Grant, Susan D Brain, Philip J Lowry, and Jonathan M Gibbins*
School of Animal & Microbial Sciences, The University of Reading, Reading, Berkshire, United Kingdom
Centre for Cardiovascular Biology and Medicine, King's College, London, United Kingdom
* Corresponding author; email: j.m.gibbins{at}reading.ac.uk.
Evidence has been mounting for peripheral functions for tachykinins, a family of neuropeptides including substance P (SP), neukokinin A and neurokinin B which are recognised for their roles in the central and peripheral nervous system. The recent discovery of four new members of this family, the endokinins (EKA, B, C and D), which are distributed peripherally, adds support to the notion that tachykinins have physiological/endocrine roles in the periphery. In the present study we report a fundamental new function for tachykinins in the regulation of platelet function. We show that SP stimulates platelet aggregation, and underlying this is the intracellular mobilisation of calcium and degranulation. We demonstrate the presence of the tachykinin receptors NK1 and NK3 in platelets and present evidence for the involvement of NK1 in SP mediated platelet aggregation. Platelets were found to contain SP-like immunoreactivity that is secreted upon activation implicating SP-like substances in the autocrine/paracrine regulation of these cells. Indeed, NK1-blocking antibodies inhibited aggregation in response to other agonists. Of particular note is the observation that EKA/B cross react in the SP immunoassay and are also able to stimulate platelet activation. Together our data implicate tachykinins, specifically SP and EKA/B in the regulation of platelet function.

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