REGULATION OF SEROTONIN(2A) RECEPTORS IN HETEROLOGOUS EXPRESSION SYSTEMS

The serotonin(2A) and serotonin,e receptors are unique among receptors coupled to guanine nucleotide binding proteins in that chronic treatm ent in vivo with agonists as well as antagonists decreases receptor de nsity. In an attempt to uncover molecular events involved in down-regu lation of the serotonin(2A) receptor, the ability of agonists and anta gonists to alter receptor density was examined in three heterologous e xpression systems, i.e., transfected NIH 3T3, transfected Madin-Darby canine kidney, and transfected AtT-20 cells. All three transfected cel l lines exhibited pharmacological properties consistent with that pred icted for cells expressing the serotonin,A receptor. However, the thre e cell lines displayed different receptor regulation properties in res ponse to drugs acting al the serotonin(2A), receptor. In transfected N IH 3T3 cells, neither agonist nor antagonist treatment altered recepto r density. Treatment with agonist as well as antagonist led to up-regu lation of the serolonin,, receptor in transfected Madin-Darby canine k idney cells. In transfected AtT-20 cells, treatment with agonist led t o receptor down-regulation, whereas antagonist treatment increased rec eptor density. Thus, the cellular background in which the seretonin(2A ) receptor is expressed appears to determine the regulation properties of the receptor.