Introduction

Abstract

The discovery of non-adrenergic, non-cholinergic neurotransmission in the gut and bladder in the early 1960’s is described and the identification of ATP as a transmitter in these nerves in the early 1970’s. The concept of purinergic cotransmission was formulated in 1976 and it is now recognized that ATP is a cotransmitter in all nerves in the peripheral and central nervous systems. Two families of receptors to purines were recognized in 1978, P1 (adenosine) receptors and P2 receptors sensitive to ATP and ADP. Cloning of these receptors in the early 1990’s was a turning point in the acceptance of the purinergic signaling hypothesis and there are currently 4 subtypes of P1 receptors, 7 subtypes of P2X ion channel receptors, and 8 subtypes of P2Y G protein-coupled receptors. Both short-term purinergic signaling in neurotransmission, neuromodulation and neurosecretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation, motility, death in development, and regeneration are recognized. There is now much known about the mechanisms underlying ATP release and extracellular breakdown by ecto-nucleotidases. The recent emphasis on purinergic neuropathology is discussed, including changes in purinergic cotransmission in development and ageing and in bladder diseases and hypertension. The involvement of neuron-glial cell interactions in various diseases of the CNS, including neuropathic pain, trauma, and ischemia, neurodegenerative diseases, neuropsychiatric disorders, and epilepsy is also considered