ergoline and methoxygramine

The effect of ligand pretreatment on human 5-hydroxytryptamine2C (5-HT2C) receptors was examined in CHO cells expressing high (CHO-1C7; 67+/-3 pmol/mg) or low (CHO-1C19; 72+/-10 fmol/mg) levels of the receptor. Seventy-two hours pretreatment of CHO-1C7 cells with various ligands did not affect receptor expression. Pretreatment with inverse agonists enhanced 5-HT-mediated inositol phosphate accumulation with no change in constitutive receptor activity. The enhanced agonist responsiveness was inversely correlated with the intrinsic activity of the pretreatment ligand. Seventy-two hours of pretreatment with the weak agonist, 5-methoxygramine, caused an elevation in constitutive activity but no alteration in 5-HT-mediated signaling. In CHO-1C19 cells, 24 but not 72 h of pretreatment with the inverse agonist mianserin enhanced 5-HT-mediated signaling, with no effect on basal signaling; pretreatment with 5-methoxygramine had no significant effect. These findings highlight differences in the pattern of chronic regulation of 5HT2C receptor signaling between high and low receptor expression levels in a common cellular background.

Topics: Algorithms; Analysis of Variance; Animals; Binding, Competitive; Cell Membrane; Chlorpromazine; CHO Cells; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Ergolines; Humans; Indoles; Indophenol; Inositol Phosphates; Kinetics; Ligands; Lisuride; Mianserin; Radioligand Assay; Receptor, Serotonin, 5-HT2C; Ritanserin; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Tritium; Tryptamines