A comparative study of Kakkon-to and Keishi-to on prostaglandin E(2) release from rabbit astrocytes

The effects of Kakkon-to (Ge-Ge-Tang) and Keishi-to (Gui-Zhi-Tang), Kampo medicines, on prostaglandin E(2) (PGE(2)) release were examined in rabbit astrocytes, in order to clarify their pharmacological properties as antipyretics. Rabbit astrocytes released PGE(2) in response to bradykinin. Short term (10 min) treatment of the cells with Kakkon-to, Keishi-to or aspirin resulted in reduction of bradykinin-induced PGE(2) release. However, long term (18 h) treatment of the cells with Kakkon-to resulted in augmentation of bradykinin-induced PGE(2) release after washing out Kakkon-to in the culture medium. In contrast, long term treatment with Keishi-to or aspirin resulted in inhibition of bradykinin-induced PGE(2) release after washing out the medicine in the culture medium. These results suggest that 1 ) Kakkon-to and Keishi-to contain active substance(s) that inhibit prostaglandin synthesis, and 2) long term treatment of the cells with Kakkon-to elicits changes on the cellular responses to bradykinin, but Keishi-to as well as aspirin irreversibly blocks the enzymes involved in PGE(2) synthesis.