Adenosine and its receptors, pathophysiological significance and therapeutic opportunities.
The focus of our research is on adenosine receptors and on the actions of the most widely used of all psychoactive drugs, caffeine, which acts as an inhibitor at these receptors. There are four cloned forms of adenosine receptors and their pharmacological characteristics are examined using CHO cells that express the human A1, A2A, A2B and A3 receptors. The signaling properties of the receptors are studied in the same cells, but also in several types of cells where they are naturally expressed.
The cultured cells also lend themselves to studies of how the different receptors are regulated, at the transcriptional and posttranscriptional level.
By in situ hybridization, immunocytochemistry and receptor autoradiography the distribution of the receptors in tissues and cells is studied. In particular we examine their ontogeny and how the local expression of the receptors is altered by long, or short-term drug treatment or physiological changes.
The natural ligand, adenosine, is a modulator rather than a transmitter or a hormone, and it is therefore important to examine how the adenosine receptors influence signaling mediated via other receptors. Considerable effort is spent on elucidating the interactions between co expressed A2A and dopamine D2 receptors, because this interaction is a key to the central actions of caffeine. In recent years our efforts have been concentrated on elucidating the pathophysiological roles of adenosine using receptor knockouts.