To begin defining the factors regulating neurotransmitter receptor expression, we examined beta-adrenergic receptors in rat liver in vivo and in primary liver cultures under defined hormonal conditions. P-receptors described a remarkable developmental profile in vivo, increasing fivefold between embryonic days 16 and 20, and decreasing tenfold by early adulthood. The developmental decrease reflected reduced receptor number without a change in receptor properties. The ontogenetic decrease appeared to be specific for P-receptors; a-receptors developed in a hyperbolic fashion, reaching high plateau values by the third postnatal week.
Adult rat liver cells plated into culture re-expressed high (3-receptor levels, exhibiting a 4-8-fold increase. A similar pattern of expression of the P-receptors, having similar pharmacological properties, was observed in primary liver cultures maintained in serum-free medium, in a serum-supplemented medium or in several variations of a serum-free, hormonally defined medium designed for primary liver cultures. Thus, the degree of expression of the P-receptors was not found affected by various hormones, by serum, or by any medium condition. By contrast, the degree of expression of the P-receptors was markedly sensitive to cell density. High expression of the P-receptors was observed at low cell densities (1-3 x 106 cellsi150 mm dish), and low expression or no expression was observed in confluent cultures (1 0-20 x 1 O6 cells/150 mm dish). Our experiments suggest that P-receptor expression does not follow an immutable program, but may be regulated by density-dependent cell-cell interactions.