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Review Article

Pathophysiology and Therapeutic Potential of Purinergic Signaling

Autonomic Neuroscience Centre, Royal Free and University College Medical School, London, United Kingdom

Abstract

I. Introduction

II. Cardiovascular Diseases

A. Thrombosis

B. Heart Failure

C. Hypertension

D. Atherosclerosis and Restenosis

III. Neurology

A. Neuroprotection

B. Migraine

C. Pain

D. Diseases of Special Senses

1. Eye.

2. Ear.

3. Nasal Organs.

IV. Immune System and Inflammation

V. Endocrinology, Diabetes, and Obesity

A. Diabetes

B. Obesity

VI. Gastroenterology

VII. Urogenital Diseases

A. Kidney and Ureter

B. Lower Urinary Tract

C. Reproductive System

VIII. Dermatology

IX. Respiratory Diseases

X. Musculoskeletal Diseases

XI. Oncology

XII. Future Developments

The concept of a purinergic signaling system, using purine nucleotides and nucleosides as extracellular messengers, was first proposed over 30 years ago. After a brief introduction and update of purinoceptor subtypes, this article focuses on the diverse pathophysiological roles of purines and pyrimidines as signaling molecules. These molecules mediate short-term (acute) signaling functions in neurotransmission, mechanosensory transduction, secretion and vasodilatation, and long-term (chronic) signaling functions in cell proliferation, differentiation, and death involved in development and regeneration. Plasticity of purinoceptor expression in pathological conditions is frequently observed, including an increase in the purinergic component of autonomic cotransmission. Recent advances in therapies using purinergic-related drugs in a wide range of pathological conditions will be addressed with speculation on future developments in the field.

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