Prolonged Treatment with Ligands Affects Ligand Binding to the Human Serotonin1A Receptor in Chinese Hamster Ovary Cells

SUMMARY 1. The serotonin_1A receptors are members of a superfamily of seven transmembrane domain receptors that couple to G-proteins, and appear to be involved in several behavioral and cognitive functions.2. We monitored the effect of prolonged treatment of the human serotonin_1A receptor expressed in Chinese hamster ovary (CHO) cells with pharmacologically well-characterized ligands on its binding to the agonist 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) and antagonist 4-(2′-methoxy)-phenyl-1-2′-(N-2″-pyridinyl)-p-fluorodobenzamido]ethyl-piperazine (p-MPPF).3. Our results indicate that prolonged treatment with the specific agonist (8-OH-DPAT) differentially affects subsequent binding of the agonist and antagonist to the receptor in a manner independent of receptor-G-protein coupling. Importantly, our results show that prolonged treatment with the commonly used antagonist p-MPPF, and its iodinated analogue 4-(2′-methoxy)-phenyl-1-2′-(N-2″-pyridinyl)-p-iodobenzamido]ethyl-piperazine (p-MPPI), which have earlier been reported to display similar binding properties to serotonin_1A receptors, induces significantly different effects on the ligand binding function of serotonin_1A receptors.