Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.657821
Title: Further characterisation of the EP4-receptor subtype
Author: Milne, S. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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Abstract:
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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.657821  DOI: Not available
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