SEQUENTIAL ONSET OF 3 5-HT RECEPTORS DURING THE 5-HYDROXYTRYPTAMINERGIC DIFFERENTIATION OF THE MURINE 1C11 CELL-LINE

1 The murine 1C11 clone, which derives from a multipotential embryonal carcinoma cell line, has the features of a neuroectodermal precursor. When cultured in the presence of dibutyryl cyclic AMP, the 1C11 cells extend bipolar extensions and express neurone-associated markers. Aft er 4 days, the resulting cells have acquired the ability to synthesize , take up, store and catabolize 5-hydroxytryptamine (5-HT). We have th us investigated the presence of 5-HT receptors during the 5-hydroxytry ptaminergic differentiation of this inducible 1C11 cell line. 2 As sho wn by the binding of [I-125]-GTI and the CGS 12066-dependent inhibitio n of the forskolin-induced cyclic AMP production, functional 5-HT1B/1D receptors become expressed on day 2 of 1C11 cell differentiation. The density of these receptors remained unchanged until day 4. 3 The same holds true for the 5-HT2B receptor, also identified by its pharmacolo gical profile and its positive coupling to the phosphoinositide cascad e. 4 On day 4 of 1C11 cell differentiation, a third 5-HT receptor, pha rmacologically and functionally similar to 5-HT2A, had become induced. 5 Strikingly, the amounts of each transcript encoding 5-HT1B, 5-HT2A and 5-HT2B receptor did not vary significantly during the time course of the 1C11 5-hydroxytryptaminergic differentiation. 6 The clone 1C11 may thus provide a useful in vitro model for studying regulation(s) be tween multiple G-linked receptors as well as the possible role of 5-HT upon the expression of a complete 5-hydroxytryptamine phenotype.