Endogenous adenosine in nervous tissue, a central link between energy metab
olism and neuronal activity, varies according to behavioral state and (path
o)physiological conditions; it may be the major sleep propensity substance.
The functional consequences of activation of the four known adenosine rece
ptors, A(1), A(2A), A(2B) and A(3), are considered here. The mechanisms and
electrophysiological actions, mainly those of the A(1)-receptor, have been
extensively studied using in vitro brain-slice preparations. A(1)-receptor
activation inhibits many neurons postsynaptically by inducing or modulatin
g ionic currents and presynaptically by reducing transmitter release. A(1)-
receptors are almost ubiquitous in the brain and affect various K+ (I-leak,
I-AHP), mixed cationic (I-h), or Ca2+ currents, through activation of G(i/
o)-proteins (coupled to ion channels, adenylyl cyclase or phospholipases).
A(2A)-receptors are much more localized, their functional role in the stria
tum is only just emerging. A(2B)- and A(3)-receptors may be affected in pat
hophysiological events, their function is not yet clear. The cAMP-PKA signa
l cascade plays a central role in the regulation of both neural activity an
d energy metabolism. Under conditions of increased demand and decreased ava
ilability of energy (such as hypoxia, hypoglycemia and/or excessive neurona
l activity), adenosine provides a powerful protective feedback mechanism. I
nteraction with adenosine metabolism is a promising target for therapeutic
intervention in neurological and psychiatric diseases such as epilepsy, sle
ep, movement (parkinsonism or Huntington's disease) or psychiatric disorder
s (Alzheimer's disease, depression, schizophrenia or addiction).