Temperature-dependent interaction of the bovine hippocampal serotonin1A receptor with G-proteins

The ligand binding and G-protein coupling of the bovine hippocampal 5-HT1A receptor as a function of temperature was monitored. There is an almost complete and irreversible loss in agonist binding at 50degreesC. However, the antagonist binding is reduced only by 50%, and this could be reversed if the temperature is lowered to 25degreesC. Interestingly, the agonist binding of the 5-HT1A receptor in membranes exposed to 50degreesC is inhibited to a much lesser extent by GTP-gamma-S, a nonhydrolysable analogue of GTP, indicating uncoupling of the 5-HT1A receptor to G-proteins at 50degreesC. We propose that high temperature selectively and irreversibly inactivates G-proteins thereby affecting G-protein-receptor interaction and agonist binding of the 5-HT1A receptor.