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Blood, 15 August 2004, Vol. 104, No. 4, pp. 913. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flaumenhaft, R. Search for Related Content PubMed Articles by Flaumenhaft, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, & VASCULAR BIOLOGY Comment on Graham et al, page 1058 Platelets feel your pain Robert Flaumenhaft HARVARD MEDICAL SCHOOL Graham and colleagues have demonstrated that platelets express tachykinin receptors, respond to tachykinins such as substance P, and even secrete a substance P–like peptide. Tachykinins are a family of structurally related peptides that were originally thought to be of neuronal origin. The pre-eminent member of this family is substance P, which was identified in 1931. Neurokinins A and B; endokinins A, B, C, and D; hemokinins; and others were subsequently identified. Tachykinin receptors (NK1,NK2, and NK3) have also been identified.1 Tachykinins are widely expressed in central and peripheral nervous systems and participate in neurotransmission. Substance P and neurokinin A are required to produce moderate to severe pain.2 Over the past several years, a steadily increasing number of peripheral actions of tachykinins have been reported. Tachykinins function in airways, the gastrointestinal tract, and the urinary tract, and mediate neurogenic inflammation.3 The elaboration of high concentrations of neurokinin B by the placenta has been linked to pre-eclampsia.4 Since platelet dysfunction is associated with pre-eclampsia, Graham and colleagues addressed the possibility that platelets respond to tachykinins. The results of their studies hold a number of surprises. First, platelets aggregated and secreted granules in response to substance P. The authors demonstrated that tachykinin receptors NK1 (the preferred receptor for substance P) and NK3 (the preferred receptor for neurokinin B) are present in human platelets. Antibodies directed at NK1 impaired, but did not abrogate, platelet aggregation in response to substance P. Similarly, platelets from NK1 null mouse showed only a modestly impaired response to substance P. Thus, NK1 participates in substance P–induced platelet activation, but other receptors likely contribute as well. Another surprise was that NK1 receptors are expressed in an activation-dependent manner. For example, stimulation with thrombin resulted in a 9-fold increase in NK1 receptor surface expression. In addition, the authors found that platelets released a substance P–like peptide upon activation. The fact that platelets express tachykinin receptors and release a substance P–like peptide upon activation raised the possibility that tachykinins could behave in an autocrine/paracrine manner. To test this possibility, the authors stimulated platelets with submaximal concentrations of thrombin in the presence of antibodies directed at the NK1 receptor. Under these conditions, anti-NK1 receptor antibody inhibited thrombin-induced aggregation. Platelets from NK1 receptor–deficient mice also displayed a modest impairment of thrombin-induced aggregation induced by low thrombin concentrations. Taken together, these studies form strong evidence that tachykinins influence platelet function. Historically, platelets have served as an easily accessible cell model for neurons.5 The studies of Graham and colleagues reveal that platelets and neurons share a common set of stimulatory peptides and receptors. It is conceivable that under certain physiologic conditions tachykinins mediate cross talk between these 2 cell types. More plausibly, platelet tachykinins may participate as secondary agonists in hemostasis. The sharing of a common stimulatory axis has clinical implications. For example, do small molecule antagonists of tachykinin receptors, presently in clinical trials, represent bleeding risks? Might such therapeutics pose bleeding risks in combination with commonly used antiplatelet medications? These concerns await proof in a physiologic system that tachykinins function in hemostasis as they do in neurotransmission. References Pennefather JN, Lecci A, Candenas ML, Patak E, Pinto FM, Maggi CA. Tachykinins and tachykinin receptors: a growing family. Life Sci. 2004;74: 1445-1463.[CrossRef][Medline] [Order article via Infotrieve] Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI. Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 1998;392: 390-394.[CrossRef][Medline] [Order article via Infotrieve] Lecci A, Giuliani S, Tramontana M, Carini F, Maggi CA. Peripheral actions of tachykinins. Neuropeptides. 2000;34: 303-313.[CrossRef][Medline] [Order article via Infotrieve] Page NM, Woods RJ, Gardiner SM, et al. Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia. Nature. 2000;405: 797-800.[CrossRef][Medline] [Order article via Infotrieve] Wirz-Justice A. Platelet research in psychiatry. Experientia. 1988;44: 145-152.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: 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 Blood 2004 104: 1058-1065. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flaumenhaft, R. Search for Related Content PubMed Articles by Flaumenhaft, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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