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A comparative study of the prostanoid receptor profile of 9α11β‐prostaglandin F 2 and prostaglandin D 2
Author(s) -
Giles H.,
Bolofo M.L.,
Lydford S.J.,
Martin G.R.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12465.x
Subject(s) - prostanoid , potency , receptor , agonist , prostaglandin , chemistry , medicine , endocrinology , guinea pig , prostaglandin e2 receptor , pharmacology , biochemistry , in vitro
1 The aim of this study was to determine the receptor profile of 9α11β‐prostaglandin F 2 (PGF 2 ) and compare it with that of its parent, prostaglandin D 2 (PGD 2 ). The experiments were designed to overcome the problems associated with the presence of multiple prostanoid receptor sub‐types in most tissues; the lack of selective antagonists for each receptor means that conclusions regarding efficacy at FP and EP 2 receptors must remain provisional. 2 At DP receptors in human platelets and rabbit jugular vein, PGD 2 was a full agonist, p[A 50 ] 7.02 ± 0.09 and 6.60 ± 0.12 respectively. 9α11β‐PGF 2 was approximately 30–60 fold less potent than PGD 2 . 3 9α11β‐PGF 2 was a full agonist in the FP receptor containing preparation, cat iris sphincter (p[A 50 ] 7.35 ± 0.09) comparable in potency to PGD 2 (p[A 50 ] 7.15 ± 0.19). Likewise the two prostanoids showed similar potency at the TP receptor in guinea‐pig aorta (9α11β‐PGF 2 p[A 50 ] 6.00 ± 0.07; PGD 2 6.24 ± 0.08). 4 9α11β‐PGF 2 and PGD 2 had efficacy but low potency at EP 1 receptors (guinea‐pig oesophageal muscularis mucosa) and demonstrated 2000–3000 fold lower potency than PGE 2 (p[A 50 ] 8.35 ± 0.09). Similarly, in the EP 2 receptor‐containing preparation, cat trachea, 9α11β‐PGF 2 was 3500 fold less potent and PGD 2 700 fold less potent than PGE 2 (p[A 50 ] 8.06 ± 0.26). 5 9α11β‐PGF 2 and PGD 2 (10 μ m ) were without affinity at the IP receptors on human platelets and had no agonist action in the EP 3 receptor containing preparation, guinea‐pig vas deferens. 6 9α11β‐PGF 2 is a major metabolite of PGD 2 in vivo and this conversion clearly represents an inactivation step since 9α11β‐PGF 2 is of considerably lower potency than PGD 2 at DP receptors. However, it is of similar potency to PGD 2 at TP, FP, EP 1 and EP 2 receptors and it may, therefore, contribute to the biological effects which follow PGD 2 administration or endogenous synthesis; its actions at these receptors are likely to be similar to those of PGD 2 itself.