Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2009, Article ID 545263, 5 pages

P 2 X 7 Receptors as a Transducer in the Co-Occurrence of Neurological/Psychiatric and Cardiovascular Disorders: A Hypothesis

Department of Pharmacology and Anesthesiology, University of Padova, Largo “E.Meneghetti” 2, 35131 Padova, Italy

Received 23 May 2009; Accepted 19 June 2009

Academic Editor: Hari Manev

Copyright © 2009 Stephen D. Skaper and Pietro Giusti. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Over-stimulation of the purinergic P 2 X 7 receptor may bring about cellular dysfunction and injury in settings of neurodegeneration, chronic inflammation, as well as in psychiatric and cardiovascular diseases. Here we speculate how P 2 X 7 receptor over-activation may lead to the co-occurrence of neurological and psychiatric disorders with cardiovascular disorders. Presentation. We hypothesize that proinflammatory cytokines, in particular interleukin-1 𝛽 , are key players in the pathophysiology of neurological, psychiatric, and cardiovascular diseases. Critically, this premise is based on a role for the P 2 X 7 receptor in triggering a rise in these cytokines. Given the broad distribution of P 2 X 7 receptors in nervous, immune, and vascular tissue cells, this receptor is proposed as central in linking the nervous, immune, and cardiovascular systems. Testing. Investigate, retrospectively, whether a bidirectional link can be established between illnesses with a proinflammatory component (e.g., inflammatory and chronic neuropathic pain) and cardiovascular disease, for example, hypertension, and whether patients treated with anti-inflammatory drugs have a lower incidence of disease complications. Positive outcome would indicate a prospective study to evaluate therapeutic efficacy of P 2 X 7 receptor antagonists. Implications. It should be stressed that sufficient direct evidence does not exist at present supporting our hypothesis. However, a positive outcome would encourage the further development of P 2 X 7 receptor antagonists and their application to limit the co-occurrence of neurological, psychiatric, and cardiovascular disorders.