Regulation of beta-adrenergic receptor expression in rat liver.
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. beta-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 beta-receptors; alpha-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 beta-receptor levels, exhibiting a 4-8-fold increase. A similar pattern of expression of the beta-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 beta-receptors was not found affected by various hormones, by serum, or by any medium condition. By contrast, the degree of expression of the beta-receptors was markedly sensitive to cell density. High expression of the beta-receptors was observed at low cell densities (1-3 x 10(6) cells/150 mm dish), and low expression or no expression was observed in confluent cultures (10-20 x 10(6) cells/150 mm dish). Our experiments suggest that beta-receptor expression does not follow an immutable program, but may be regulated by density-dependent cell-cell interactions.
Schleifer
L S
LS
Department of Neurology, Cornell University Medical College, New York, New York 10021.
Black
I B
IB
Reid
L M
LM
D000367:Age Factors; D000818:Animals; D002450:Cell Communication; D002462:Cell Membrane / Q000032:analysis; D002478:Cells, Cultured; D006160:Guanosine Triphosphate / Q000494:pharmacology; D020120:Iodocyanopindolol; D008099:Liver / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D006160:Guanosine Triphosphate; D011433:Propranolol; D010869:Pindolol