Adenosine, Adenosine Receptors and the Actions of Caffeine *

Abstract

Of the known biochemical actions of caffeine, only inhibition of adenosine receptors occurs at concentrations achieved during normal human consumption of the drug. Under normal physiological conditions, adenosine is present in sufficient concentrations to activate A1 and A2a receptors. Via actions on A1 receptors, adenosine decreases neuronal firing and the release of neurotransmitters. The exact mechanisms are not known, but several possibilities are discussed. Via actions on A2a receptors, adenosine--and hence caffeine--can influence dopaminergic neurotransmission. Caffeine can induce rapid changes in gene expression and, somewhat later, marked adaptive changes. These include antiepileptic and neuroprotective changes. Thus, caffeine has a number of central effects directly or indirectly related to adenosine receptors. Some of these are potentially useful, and drug development based on the actions of caffeine should be interesting.

Coffee, caffeine and blood pressure: a critical review

“…noradrenaline, dopamine, acetylcholine, glutamate and GABA (Fredholm & Dunwiddie, 1988). The excitatory transmitter release seems to be more inhibited than that of the inhibitory ones (Fredholm, 1995). This may be related to activation of potassium channels via the A 1 receptors.…”

“…Caffeine exerts many of its actions by antagonizing adenosine receptors, of which four subtypes have been cloned and characterized (Fredholm, 1995;Olah & Stiles, 1995). Adenosine dilates several vascular beds (Ohah & Stiles, 1995).…”

“…Thus, caffeine may cause an increase in blood pressure by antagonizing this effect of adenosine. The major targets of caffeine are A 1 and A 2a receptors, which can be blocked by caffeine at low micromolar concentrations similar to those that occur in plasma after consumption of a few cups of coffee (Fredholm, 1995). In normotensive men, intravenous caffeine has been shown to reduce the hemodynamic effects of adenosine infusion .…”

“…Stimulation of A 1 receptors causes the inhibition of adenylate cyclase and some types of calcium channels, and the activation of several types of potassium channels, as well as phospholipases C and D (Fredholm, 1995;Olah & Stiles, 1995). Stimulation of A 2a receptors activates adenylate cyclase and probably voltage-sensitive calcium channels.…”

“…Stimulation of A 2a receptors activates adenylate cyclase and probably voltage-sensitive calcium channels. The two subtypes of receptors may be co-expressed and activated simultaneously in the same cells (Fredholm, 1995). The actions of caffeine are therefore complicated.…”