The role of adenosine triphosphate in migraine.
Classical migraine is associated with two distinct phases; an initial vasoconstriction followed by vasodilatation. The "purinergic" hypothesis for migraine was originally put forward in 1981 as a basis for the reactive hyperaemia and pain during the headache phase. It was suggested that adenosine 5'-triphosphate (ATP) and its breakdown products adenosine 5'-monophosphate and adenosine were strong contenders for mediating the vasodilatation following the initial vasospasm and subsequent hypoxia. ATP was also implicated in the pathogenesis of pain during migraine via stimulation of primary afferent nerve terminals located in the cerebral vasculature. Recent studies have shown that the ATP-induced cerebral vasodilation is endothelium-dependent via activation of P2Y-purinoceptors on the endothelial cell surface and subsequent release of endothelium-derived relaxing factor (EDRF); and that the endothelial cells are the main local source of the ATP involved, although adenosine 5'-diphosphate and ATP released from aggregating platelets may also contribute to this vasodilatation. These findings have extended the "purinergic" hypothesis for migraine in two ways. Firstly, they have clarified the mechanism of purinergic vasodilatation during the headache phase of migraine. Secondly, they suggest that a purinergic mechanism may also be involved in the initial local vasospasm, via P2X-purinoceptors on smooth muscle cells occupied by ATP released either as a cotransmitter with noradrenaline from perivascular sympathetic nerves or from damaged endothelial cells.
Burnstock
G
G
Department of Anatomy and Developmental Biology, University College London, UK.
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000502:physiology; D002560:Cerebrovascular Circulation; D006801:Humans; D008881:Migraine Disorders / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D010974:Platelet Aggregation; D011983:Receptors, Purinergic / Q000502:physiology; D014661:Vasoconstriction; D014664:Vasodilation
D011983:Receptors, Purinergic; D009569:Nitric Oxide; D000255:Adenosine Triphosphate