Direct noncompetitive inhibition of 5-HT3 receptor-mediated responses by forskolin and steroids

M. Oz, L. Zhang, C. E. Spivak

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36 Citations (Scopus)


5-HT3 receptors cloned from NCB-20 cells were expressed in Xenopus oocytes, and the effects of forskolin and steroids on the function of the receptors were investigated using the two-electrode voltage-clamp technique. Forskolin, 17-β-estradiol, and progesterone inhibited the currents activated by 1 μM 5-HT in a reversible and concentration-dependent manner, with IC50 values of 12, 33, and 89 μM, respectively. The inhibitory effects of forskolin and 17-β-estradiol were independent of the membrane potential. Forskolin and 17-β-estradiol significantly reduced the maximal amplitude of the 5-HT concentration-response curve (Emax) without significantly affecting the EC50, indicating that these compounds act as noncompetitive inhibitors of the 5-HT3 receptor. The cAMP analogue, 8-Br-cAMP (0.2mM), and the protein kinase A activator, Sp-cAMP (0.1 mM), did not affect the amplitude of 5-HT3 receptor-mediated currents. The membrane-permeable protein kinase A inhibitor Rp-cAMP (0.1 mM) and the estrogen-receptor antagonist tamoxifen (1 μM) did not affect the inhibition of 5-HT-activated current. In addition, 5-HT3 receptor-mediated currents were inhibited by both 1,9-dideoxy forskolin (30 μM), which does not activate adenylyl cyclase, and wForskolin (30 μM), a charged hydrophilic analogue of forskolin that is membrane impermeable. These results indicate that both forskolin and 17-β3-estradiol inhibit the function of the 5-HT3 receptor in a noncompetitive manner and that this inhibition is independent of cAMP levels.

Original languageEnglish
Pages (from-to)293-301
Number of pages9
JournalArchives of Biochemistry and Biophysics
Issue number2
Publication statusPublished - Aug 15 2002
Externally publishedYes


  • 5-HT receptor
  • CyclicAMP
  • Forskolin
  • Steroids
  • Xenopus oocyte

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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