Adenosine A2A receptor interactions with receptors for other neurotransmitters and neuromodulators

Adenosine, by activating adenosine A2A receptors, seems to have a crucial function in regulating the activation of multiple receptors that affect neurotransmitter release and/or synaptic transmission, in particular receptors for neuropeptides (calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP)), and NMDA receptors, metabotropic glutamate receptors, nicotinic autofacilitatory receptors, dopamine receptors and adenosine A1 receptors. The manner in which these A2A receptors are involved in interactions with the receptors for other neurotransmitters and or neuromodulators opens novel avenues for the action of this 'omnipresent' nucleoside. Either by direct receptor-receptor modulation or by post-receptor mechanisms, adenosine, in its 'obsession' to protect cells from insults, uses as many receptor systems as possible to synchronize synaptic transmission, in order to exert what seems to be the 'destiny' of this nucleoside--protection of the nervous system.