Abstract

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 μM 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.

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