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Prostaglandin E 2  (PGE 2 ) has been shown to dilate and constrict the systemic vascular beds, including cerebral vessels. The exact mechanism of PGE 2 -induced cerebral vasoconstriction, however, is less clarified. The authors' preliminary studies showed that PGE 2  exclusively constricted the adult porcine basilar arteries. The present study, therefore, was designed to examine the receptor mechanisms involved in PGE 2 -induced constriction of large cerebral arteries in the adult pig. Results from an in vitro tissue-bath study indicated that PGE 2  and its agonists 17-phenyl trinor PGE 2  (17-PGE 2 ), sulprostone (EP 1 /EP 3  receptor agonists), and 11-deoxy-16,16-dimethyl PGE 2  (11-PGE 2 , an EP 2 /EP 3 -receptor agonist) induced exclusive constriction, which was not affected by endothelium denudation or cold-storage denervation of perivascular nerves. The constriction induced by PGE 2 , 17-PGE 2 , and sulprostone, but not by potassium chloride, was blocked by SC-19220 (a selective EP 1 -receptor antagonist), AH-6809 (an EP 1 /EP 2 -receptor antagonist), and U-73122 and neomycin (phospholipase C inhibitors). AH-6809, however, did not affect 11-PGE 2 –induced contraction. These results suggest that the contraction was not mediated by the EP 2 -receptor, but was mediated by EP 1 - and EP 3 -receptors. Furthermore, EP 1 -receptor immunoreactivities were found across the entire medial smooth muscle layers, whereas EP 3 -receptor immunoreactivities were limited to the outer smooth muscle layer toward the adventitia. Western blotting also showed the presence of EP 1 - and EP 3 -receptor proteins in cultured primary cerebral vascular smooth muscle cells. In conclusion, PGE 2  exclusively constricts the adult porcine large cerebral arteries. This constriction is mediated by phosphatidyl–inositol pathway via activation of EP 1 - and EP 3 -receptors located on the smooth muscle cells. These two receptor subtypes may play important roles in physiologic and pathophysiologic control of cerebral vascular tone.

EP1- and EP3-Receptors Mediate Prostaglandin E2–Induced Constriction of Porcine Large Cerebral Arteries

EP₁- and EP₃-Receptors Mediate Prostaglandin E₂–Induced Constriction of Porcine Large Cerebral Arteries