A comparative study of the prostanoid receptor profile of 9 alpha 11 beta-prostaglandin F2 and prostaglandin D2.
1. The aim of this study was to determine the receptor profile of 9 alpha 11 beta-prostaglandin F2 (PGF2) and compare it with that of its parent, prostaglandin D2 (PGD2). 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 EP2 receptors must remain provisional. 2. At DP receptors in human platelets and rabbit jugular vein, PGD2 was a full agonist, p[A50] 7.02 +/- 0.09 and 6.60 +/- 0.12 respectively. 9 alpha 11 beta-PGF2 was approximately 30-60 fold less potent than PGD2. 3. 9 alpha 11 beta-PGF2 was a full agonist in the FP receptor containing preparation, cat iris sphincter (p [A50] 7.35 +/- 0.09) comparable in potency to PGD2 (p[A50] 7.15 +/- 0.19). Likewise the two prostanoids showed similar potency at the TP receptor in guinea-pig aorta (9 alpha 11 beta-PGF2 p[A50] 6.00 +/- 0.07; PGD2 6.24 +/- 0.08). 4. 9 alpha 11 beta-PGF2 and PGD2 had efficacy but low potency at EP1 receptors (guinea-pig oesophageal muscularis mucosa) and demonstrated 2000-3000 fold lower potency than PGE2 (p[A50] 8.35 +/- 0.09). Similarly, in the EP2 receptor-containing preparation, cat trachea, 9 alpha 11 beta-PGF2 was 3500 fold less potent and PGD2 700 fold less potent than PGE2 (p[A50] 8.06 +/- 0.26). 5. 9 alpha 11 beta-PGF2 and PGD2 (10 microM) were without affinity at the IP receptors on human platelets and had no agonist action in the EP3 receptor containing preparation, guinea-pig vas deferens. 6. 9 alpha 11 beta,-PGF2 is a major metabolite of PGD2 in vivo and this conversion clearly represents an inactivation step since 9 alpha 11 beta-PGF2 is of considerably lower potency than PGD2 at DP receptors. However, it is of similar potency to PGD2 at TP, FP, EP1 and EP2 receptors and it may, therefore, contribute to the biological effects which follow PGD2 administration or endogenous synthesis; its actions at these receptors are likely to be similar to those of PGD2 itself.
Giles
H
H
Analytical Pharmacology Group, Wellcome Research Laboratories, Beckenham, Kent.
Bolofo
M L
ML
Lydford
S J
SJ
Martin
G R
GR
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002415:Cats; D003627:Data Interpretation, Statistical; D015237:Dinoprost / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D009130:Muscle, Smooth / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000145:classification / Q000378:metabolism*; D018078:Receptors, Prostaglandin E
D011458:Prostaglandins E; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor