부산대학교 도서관

The Rabbit Jugular vein (RJV) and Pig Saphenous vein (PSV) were used to further characterise the EP₄-receptor. Organ bath studies with an array of EP-agonists and antagonists produced data which confirmed the PSV as an EP₄-receptor containing preparation and that the RJV, after comparing agonist potency profiles, also contained the EP₄-receptor subtype. The agonist potency profile obtained was PGF₂ ≥ 11-deoxy PGE₁ = 16, 16-dimethyl PGE₂ > butaprost >> AH13205. The Chinese Hamster Ovary (CHO) cell line was used as an alternative to the smooth muscle cells to study the EP4-receptor subtype. Studies using the effects of EP-agonists and an EP-antagonist AH23848 on cyclic AMP production confirmed that the cell line expressed the EP₄-receptor. Binding studies were attempted with CHO cell membranes but were inconclusive. Mononuclear phagocytic cells (monocytes) originate in the bone marrow, are resident in the blood and migrate to tissues where they differentiate into macrophages. Monocyte/macrophages are phagocytic cells which release many substances including reactive oxygen metabolites such as superoxide anion and cytokines such as IL-1α and IL-1β when stimulated. PGE₂ has been shown to have an inhibitory effect on monocytes and the characterisation of the EP-receptor subtype(s) was attempted and the second messenger pathway was investigated. In human monocytes tested with an array of EP-agonists and antagonists, cAMP measurements indicated the involvement of the EP₄ receptor giving a similar agonist potency profile as the smooth muscle studies. Further studies measuring IL-1α and IL-1β showed PGE₂ to have an inhibitory effect but were unable to classify the receptor involved. Superoxide anion generation measurement from the human monocyte showed PGE₂ to have an inhibitory effect in the human monocyte although it did not indicate which EP-receptor was involved. Second messenger studies using this preparation showed cAMP to be involved in PEG₂ mediated inhibition of superoxide anion generation.