The coumarin osthol attenuates the binding of thyrotropin-releasing hormone in rat pituitary GH4C1 cells.
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 Ca(2+)-free buffer. Binding experiments with [3H]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.
Ojala
T
T
Department of Pharmacy, Division of Pharmacognosy, University of Helsinki, Finland.
Vuorela
P
P
Vuorela
H
H
Törnquist
K
K
D000818:Animals; D019661:Apiaceae / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007553:Isotope Labeling; D008730:Methoxsalen / Q000302:isolation & purification / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000032:analysis; D008517:Phytotherapy; D010902:Pituitary Gland / Q000187:drug effects; D011188:Potassium / Q000493:pharmacokinetics; D051381:Rats; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D014316:Tritium
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D003374:Coumarins; D010716:Phosphatidylinositols; D018025:Receptors, Thyrotropin-Releasing Hormone; D014316:Tritium; D013973:Thyrotropin-Releasing Hormone; D011188:Potassium; D002118:Calcium; D008730:Methoxsalen; C046627:osthol