Functions of neuronal adenosine receptors

Citation
Hl. Haas et O. Selbach, Functions of neuronal adenosine receptors, N-S ARCH PH, 362(4-5), 2000, pp. 375-381
Citations number
76
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Pharmacology & Toxicology
Journal title
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
ISSN journal
0028-1298 → ACNP
Volume
362
Issue
4-5
Year of publication
2000
Pages
375 - 381
Database
ISI
SICI code
0028-1298(200011)362:4-5<375:FONAR>2.0.ZU;2-D
Abstract
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).