Molecular and pharmacological characterization of zebrafish 'contractile' and 'inhibitory' prostanoid receptors

Ryo Iwasaki, Kyoshiro Tsuge, Kazushi Morimoto, Tomoaki Inazumi, Osamu Kawahara, Atsuo Kawahara, Soken Tsuchiya, Yukihiko Sugimoto

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Prostanoids comprising prostaglandins (PGs) and thromboxanes (TXs) have been shown to play physiological and pathological roles in zebrafish. However, the molecular basis of zebrafish prostanoid receptors has not been established. Here, we demonstrate that there exist at least five 'contractile' (Ca2+-mobilizing) and one 'inhibitory' (Gi-coupled) prostanoid receptors in zebrafish; five 'contractile' receptors consisting of two PGE2 receptors (EP1a and EP1b), two PGF receptors (FP1 and FP2), and one TXA2 receptor TP, and one 'inhibitory' receptor, the PGE2 receptor EP3. [3H]PGE2 specifically bound to the membranes of cells expressing zebrafish EP1a, EP1b and EP3 with a Kd of 4.8, 1.8 and 13.6nM, respectively, and [3H]PGF specifically bound to the membranes of cells expressing zebrafish FP1 and FP2, with a Kd of 6.5 and 1.6nM, respectively. U-46619, a stable agonist for human and mouse TP receptors, significantly increased the specific binding of [35S]GTPγS to membranes expressing the zebrafish TP receptor. Upon agonist stimulation, all six receptors showed an increase in intracellular Ca2+ levels, although the increase was very weak in EP1b, and pertussis toxin abolished only the EP3-mediated response. Zebrafish EP3 receptor also suppressed forskolin-induced cAMP formation in a pertussis toxin-sensitive manner. In association with the low structural conservation with mammalian receptors, most agonists and antagonists specific for mammalian EP1, EP3 and TP failed to work on each corresponding zebrafish receptor. This work provides further insights into the diverse prostanoid actions mediated by their receptors in zebrafish.

Original languageEnglish
Pages (from-to)353-358
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume438
Issue number2
DOIs
Publication statusPublished - Aug 23 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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