Biological insights from the direct measurement of purine release

Although purinergic signalling has been a well-established and accepted mechanism of chemical communication for many years, it remains important to measure the extracellular concentration of ATP and adenosine in real time. In this review I summarize the reasons why such measurements are still needed, how they provide additional mechanistic insight and give an overview of the techniques currently available to make spatially localised measurements of ATP and adenosine in real time. To illustrate the impact of direct real-time measurements, I explore CO₂ and nutrient sensing in the medulla oblongata and hypothalamus. In both of these examples, the sensing involves hemichannel mediated ATP release from glial cells. For CO₂ the hemichannels involved, connexin26, are directly CO₂-sensitive. This mechanism contributes to the chemosensory control of breathing. In the hypothamalus, specialised glial cells, tanycytes, directly contact the cerebrospinal fluid in the 3rd ventricle and sense nutrients via sweet and umami taste receptors. Nutrient sensing by tanycytes is likely to contribute to the control of body weight as their selective stimulation alters food intake. To illustrate the importance of direct adenosine measurements, I consider the complex and multiple mechanisms of activity-dependent adenosine release in different brain regions. This activity dependent release of adenosine is likely to mediate important feedback regulation and may also be involved in controlling the sleep-wake state. I finish by briefly considering the potential of whole blood purine measurements in clinical practice.