P2X(7) Receptors as a Transducer in the Co-Occurrence of Neurological/Psychiatric and Cardiovascular Disorders: A Hypothesis.

Background. Over-stimulation of the purinergic P2X(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 P2X(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-1beta, are key players in the pathophysiology of neurological, psychiatric, and cardiovascular diseases. Critically, this premise is based on a role for the P2X(7) receptor in triggering a rise in these cytokines. Given the broad distribution of P2X(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 P2X(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 P2X(7) receptor antagonists and their application to limit the co-occurrence of neurological, psychiatric, and cardiovascular disorders.