Non-competitive inhibition of 5-HT3 receptor-mediated currents by progesterone in rat nodose ganglion neurons.
The effect of progesterone on the serotonin type 3 (5-HT3) receptor-mediated response was studied in acutely dissociated rat nodose ganglion neurons by using the whole-cell voltage-clamp technique. Progesterone rapidly and reversibly inhibited 5-HT-induced currents in a dose-dependent manner, with an EC50 of 31 microM and a maximal inhibition of 75%. Neither the 5-HT response nor inhibition of the 5-HT response by extracellularly applied progesterone was significantly affected by inclusion of a saturating concentration of progesterone in the electrode buffer, arguing that progesterone acted at the extracellular surface of the membrane. Progesterone also inhibited the 5-HT response non-competitively by a voltage- and agonist-independent mechanism that was distinct from that of open-channel blockers.
Wu
F S
FS
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. fongsen@mail.ncku.edu.tw
Lai
C P
CP
Liu
B C
BC
D000818:Animals; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D011374:Progesterone