EP 4 prostanoid receptor‐mediated vasodilatation of human middle cerebral arteries

Dilatation of the cerebral vasculature is recognised to be involved in the pathophysiology of migraine. Furthermore, elevated levels of prostaglandin E 2 (PGE 2 ) occur in the blood, plasma and saliva of migraineurs during an attack, suggestive of a contributory role. In the present study, we have characterised the prostanoid receptors involved in the relaxation and contraction of human middle cerebral arteries in vitro . In the presence of indomethacin (3 μ M ) and the TP receptor antagonist GR32191 (1 μ M ), PGE 2 was found to relax phenylephrine precontracted cerebral arterial rings in a concentration‐dependent manner (mean pEC 50 8.0±0.1, n =5). Establishment of a rank order of potency using the EP 4 >EP 2 agonist 11‐deoxy PGE 1 , and the EP 2 >EP 4 agonist PGE 1 ‐OH (mean pEC 50 of 7.6±0.1 ( n =6) and 6.4±0.1 ( n =4), respectively), suggested the presence of functional EP 4 receptors. Furthermore, the selective EP 2 receptor agonist butaprost at concentrations