The Coumarin Osthol Attenuates the Binding of Thyrotropin-Releasing Hormone in Rat Pituitary GH4C1 Cells

Abstract

The influence of two plant coumarins, osthol and xanthotoxin, on intracellular Ca²⁺ ([Ca²⁺]_i) transients evoked by TRH were studied in clonal rat pituitary GH₄C₁ cells. Osthol, but not xanthotoxin, decreased the TRH-induced transient increase in [Ca²⁺]_i in Fluo-3 loaded cells incubated in Ca²⁺-free buffer. Binding experiments with [³ H]TRH showed that osthol decreased the binding of TRH to its receptor, whereas the affinity of the receptor for TRH increased. This resulted in a decreased TRH-evoked production of IP₃ in cells treated with osthol, and a decreased mobilization of sequestered calcium. Osthol did not inhibit the release of calcium evoked by exogenous IP₃ in permeabilized cells. Furthermore, osthol decreased the uptake of ⁴⁵Ca²⁺ in response to high K⁺. Xanthotoxin had no effects in these experiments. The results show that osthol modulates TRH-evoked responses by interacting with the TRH receptor.

Key words

GH₄C₁ cells - coumarins - thyrotropin-releasing hormone (TRH)

References

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