Adenosine Stimulated Respiration and Pain in Man: Examples of Adenosine Receptor Modulated Afferent Information

Abstract

Cellular adenosine formation and release is enhanced by hypoxia or lack of energy supply. Adenosine acts in several ways to balance the supply to the cellular demands. In 1929 Drury and Szent-Györgyi showed that adenosine produced several biological effects such as hypotension and bradycardia. Since then different effects of adenosine have been studied. For example, apart from its vasodilatory effect adenosine inhibits lipolysis, aggregation of platelets, release of noradrenaline and acetylcholine, hippocampal pyramidal excitability, motor behaviour and even respiration. Some of the actions of adenosine may be due to uptake into cells and further metabolic effects but most of the effects are mediated via specific adenosine cell surface receptors. Methylxanthines such as caffeine and theophylline, in the clinical relevant concentration range, act as competetive adenosine receptor antagonists (for review see Fredholm and Jonzon 1987). Adenosine is rapidly eliminated mainly by cellular uptake. The half life of adenosine in blood is approximately 10 seconds. Dipyridamole blocks the carrier mediated transport of adenosine across the cell membrane and thereby enhances the extracellular concentration and the receptor mediated effects of administered adenosine. We have studied the respiratory stimulation and estimated the pain response of bolus injections of adenosine to humans.