Caffeine inhibits the binding of thyrotropin-releasing hormone in GH4C1 pituitary cells.
Caffeine can modulate intracellular Ca2+ concentration ([Ca2+]i) by triggering the mobilization of Ca2+ from intracellular Ca2+ stores. In the present study we show that in Fura 2 loaded GH4C1 cells, caffeine inhibited, in a dose-dependent manner, the Ca2+ response induced by a submaximally effective dose (3 nM) of thyrotropin-releasing hormone (TRH). We also show that caffeine decreased the specific binding of [3H]TRH. Equilibrium binding studies with [3H]TRH and Scatchard analysis of the binding data showed that caffeine increased the dissociation constant (Kd) from 8 +/- 1 nM to 26 +/- 3 nM, while the maximum amount of [3H]TRH bound to the cells was increased by 32%. Thus, caffeine inhibited the TRH-evoked increase in [Ca2+]i by inhibiting the binding of TRH to its receptor.
Karhapää
L
L
Department of Biosciences, University of Helsinki, Finland.
Törnquist
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D009553:Nimodipine / Q000494:pharmacology; D010902:Pituitary Gland; D011485:Protein Binding; D051381:Rats; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology*
D018025:Receptors, Thyrotropin-Releasing Hormone; D005576:Colforsin; D002110:Caffeine; D015759:Ionomycin; D009553:Nimodipine; D013973:Thyrotropin-Releasing Hormone; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine