CIRCADIAN VARIATIONS OF ADENOSINE AND OF ITS METABOLISM - COULD ADENOSINE BE A MOLECULAR OSCILLATOR FOR CIRCADIAN-RHYTHMS

The present review describes the biological implications of the period ic changes of adenosine concentrations in different tissues of the rat . Adenosine is a purine molecule that could have been formed in the pr ebiotic chemical evolution and has been preserved. The rhythmicity of this molecule, as well as its metabolism and even the presence of spec ific receptors, suggests a regulatory role in eukaryotic cells and in multicellular organisms. Adenosine may be considered a chemical messen ger and its action could take place at the level of the same cell (aut ocrine), the same tissue (paracrine), or on separate organs (endocrine ). Exploration of the circadian variations of adenosine was planned co nsidering the liver as an important tissue for purine formation, the b lood as a vehicle among tissues, and the brain as the possible accepto r for hepatic adenosine or its metabolites. The rats used in these stu dies were adapted to a dark-light cycle of 12 h with an unrestrained f eeding and drinking schedule. The metabolic control of adenosine conce ntration in the different tissues studied through the 24-h cycle is re lated to the activity of adenosine-metabolizing enzymes: 5'-nucleotida se adenosine deaminase, adenosine kinase, and S-adenosylhomocysteine h ydrolase. Some possibilities of the factors modulating the activity of these enzymes are commented upon. The multiphysiological action of ad enosine could be mediated by several actions: (i) by interaction with extracellular and intracellular receptors and (ii) through its metabol ism modulating the methylation pathway, possibly inducing physiologica l lipoperoxidation, or participating in the energetic homeostasis of t he cell. The physiological meaning of the circadian variations of aden osine and its metabolism was focused on: maintenance of the energetic homeostasis of the tissues, modulation of membrane structure and funct ion, regulation of fasting and feeding metabolic pattern, and its part icipation in the sleep-wake cycle. From these considerations, we sugge st that adenosine could be a molecular oscillator involved in the circ adian pattern of biological activity in the rat.