Involvement of adenosine signaling pathway in migraine pathophysiology: a systematic review of preclinical studies

Table 1 Adenosine receptors and their functions

Receptor	Subunit	Signaling pathway
Adenosine A₁ receptor	Gα_i-subunit	Inhibits adenylate cyclase, decreases cAMP formation [20, 38], leading to activation of K_ATP channels [4, 26, 35, 39] and inactivation of BK_Ca channels [28]
Adenosine A₁ receptor	G_βγ subunits	Stimulates PLC and increases IP₃ [20, 38]
Adenosine A_2A receptor	Gα_s-subunit	Activates adenylate cyclase and increases cAMP formation [20, 38], leading to activation of K_ATP channels [27]
Adenosine A_2A receptor	Pertussis toxin insensitive Gα15 and Gα16 proteins	Activates PLC and upregulates IP₃ [20]
Adenosine A_2B receptor	Gα_s-subunit	Stimulates adenylate cyclase, increases cAMP formation [38], leading to activation of K_ATP channels [27]
Adenosine A_2B receptor	G_q subunit	Activates PLC and upregulates IP₃ [38]
Adenosine A₃ receptor	Gα_i -subunit	Inhibits adenylate cyclase and decreases cAMP [11, 20]
Adenosine A₃ receptor	G_βγ subunits	Increases the activity of PLC and PLD [38]
All		Modulates MAPK [20]

cAMP cyclic adenosine monophosphate, IP₃ inositol 1,4,5-triphosphate, MAPK mitogen-activated protein kinase, PLC phospholipase C, PLD phospholipase D

ISSN: 1129-2377