Adenosine A3 receptor (Adeno_A3_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

In addition to their role in energy metabolism, purines (especially adenosine and adenine nucleotides) produce a wide range of pharmacological effects mediated by activation of cell surface receptors. Distinct receptors exist for adenosine. In the periphery, the main effects of adenosine include vasodilation, bronchoconstriction, immunosuppresion, inhibition of platelet aggregation, cardiac depression, stimulation of nociceptive afferents, inhibition of neurotransmitter release and inhibition of the release of other factors, e.g. hormones. In the CNS, adenosine exerts a pre- and post-synaptic depressant action, reducing motor activity, depressing respiration, inducing sleep and relieving anxiety. The physiological role of adenosine is thought to be to adjust energy demands in line with oxygen supply. Many of the clinical actions of methylxanthines are thought to be mediated through antagonism of adenosine receptors. Four subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

A3 receptors are found in high levels in the testis, and in lower levels in the lung, kidney and heart. They are also found in low levels in regions of the CNS (including the cerebral cortex, striatum and olfactory bulb). The presence in high levels in the testis has led to the suggestion that it may play a role in reproduction. The A3 receptor inhibits adenylyl cyclase through a pertussis-toxin-sensitive G-protein, probably belonging to the Gi/Go class.