ADENOSINE REGULATES VIA TWO DIFFERENT TYPES OF RECEPTORS, THE ACCUMULATION OF CYCLIC AMP IN CULTURED BRAIN CELLS

TLDR

Adenosine modulates cyclic AMP levels in cultured brain cells. The study proposes naming the two adenosine receptor subtypes A1 and A2 based on their opposing effects on cyclic AMP. Adenosine produces a dual, concentration‑dependent effect on cyclic AMP in cultured brain cells—submicromolar concentrations inhibit β‑adrenergic‑induced cAMP via one receptor, while micromolar concentrations stimulate cAMP via a second receptor, with both effects blocked by methylxanthines, ribose‑dependent, and exhibiting distinct analogue potency profiles.

Abstract

Abstract— In cell cultures of glial character derived from perinatal mouse brain adenosine elicits two effects. (a) At submicromolar concentrations It inhibits the increase in the intracellular level of cyclic AMP caused by β‐adrenoceptor agonists. (b) At concentrations above micromolar it increases the level of cyclic AMP in the cultures. These two effects are mediated by two different adenosine receptors present on the outer surface of the cells. This is concluded from the following evidence. (a) Both effects are antagonized by methylxanthines but not by blockage of adenosine uptake or inhibition of phosphodiesterase activity. (b) In both cases activity depends on the integrity of the ribose moiety of the nucleotide. Substituents of the purine system are tolerated comparatively well. (c) The order of potency of adenosine analogues is different for the two effects. We suggest the name A1 receptors for those that mediate the inhibition and A2 for those that mediate the stimulation of cyclic AMP accumulation.