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Title: Characterisation of prostaglandin E receptors
Author: Matthews, Jane Simone
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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Prostaglandin (PG) E2 has been shown to act on at least three distinct receptor subtypes, designated EP1, EP2 and EP3, with recent evidence suggesting the possibility of a fourth EP-receptor subtype. Whilst good antagonists are not available, a range of PGE analogues of differing selectivity for the three receptor subtypes may be used to determine which is effective in a given system. The activity of these analogues has not yet been assessed on the putative EP4-receptor containing preparation. This research has involved the use of such compounds in an in vivo model of rabbit-skin inflammation, and biochemical studies on both platelets and cultured macrophages, to determine the subtype(s) of PGE receptor mediating the pro-inflammatory, pro-aggregatory, and anti-inflammatory effects, respectively, of PGE2. Whilst PGE2 alone had little effect on rabbit skin inflammation, potentiation of vascular permeability induced by mediators of inflammation, such as bradykinin (BK) and FMLP was observed. The potentiation has been attributed to the vasodilator activity of PGE2 which is typically mediated via the EP2-receptor subtype. However the finding that compounds with both EP2- and EP3-receptor activity were the most active, suggested that vasodilatation was not the sole mechanism of the potentiation. A comparison of the ability of PGE2 and the stable PGI2 analogue, cicaprost, to induce vasodilatation and potentiate the responses to both BK and FMLP, was consistent with this suggestion. It has since been proposed that there is an initial EP3-receptor mediated, dilatation-independent component to the potentiation of BK by PGE2.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available