Interaction of prostanoid EP3 and TP receptors in guinea-pig isolated aorta: contractile self-synergism of 11-deoxy-16,16-dimethyl PGE2

摘要: BACKGROUND AND PURPOSE Surprisingly high contractile activity was reported for 11-deoxy-16,16-dimethyl prostaglandin E 2 (DX-DM PGE ) on pig cerebral artery when used as a selective EP 3 receptor agonist. This study investigated the selectivity profile of DX-DM , focusing interaction between its and TP (thromboxane A -like) agonist activities. EXPERIMENTAL APPROACH Contraction guinea-pig trachea (EP 1 system) aorta systems) measured in conventional organ baths. KEY RESULTS Strong contraction to sulprostone 17-phenyl agonists) only seen under priming with second agent such phenylephrine, histamine or U-46619 (TP agonist). In contrast, induced strong contraction, which basis treatment (DG)-3ap antagonist) and/or BMS-180291 attributed self-synergism arising from co-activation receptors. 3/ also accounted by PGF 2α analogues (+)-cloprostenol latanoprost-FA. showed significant agonism defined antagonists SC-51322, (ONO)-5-methyl-1 AH-6809, although AH-6809 exhibited poor specificity at concentrations ≥ μM. CONCLUSIONS IMPLICATIONS self-synergism, PGE/PGF this study, may confound potency comparisons characterization prostanoid systems. The competitive antagonist be distorted variation silent/overt system different studies. relevance vivo actions natural agonists is discussed.