A role of asialoglycoproteins for plasma-membrane-induced inhibition of the switching from α1 to β subtypes in adrenergic response during primary culture of rat hepatocytes

Adrenergic responses of rat hepatocytes were studied by measuring Ins(1,4,5)P3 (for the response via α1-subtype receptors) and cAMP (for β-subtype response) generation during brief incubation of cells with respective agonists. Hepatocytes from young rats with an age of 1 week displayed a very high β response without a significant α1 response. The β response decreased and the α1 response increased progressively as the age increased; the response was almost exclusively via α1 receptors in hepatocytes of adult rats 9 weeks or more old. The β response developed, again at the expense of the α1 response, in hepatocytes from adult rats during the primary culture at low cell densities [(1–2.5)×104 cells/cm2]. Such ‘α1 to β subtype switching’ of adrenergic responses in vitro was totally inhibited by adding plasma membranes prepared from adult rat liver into the low-cell-density culture, but not inhibited at all by membranes from young rat liver. The inhibitory effect of adult rat liver membranes was lost when the membranes had been exposed to endoglycosidase F or β-galactosidase but was not affected by prior treatment with sialidase. On the contrary, young rat liver membranes became inhibitory to ‘α1 to β subtype switching’ after prior treatment with sialidase. Thus glycoproteins with unsialylated galactosyl termini on the surface of adult rat hepatocytes are likely to function as a determinant of the relative development of α1/β subtypes of adrenergic responses; the β response is predominant in hepatocytes in the juvenile, presumably as a result of sialylation of the galactosyl termini of the functional glycoproteins.