Switching from α1- to β-subtypes in adrenergic response during primary culture of adult-rat hepatocytes as affected by the cell-to-cell interaction through plasma membranes

Abstract

The α1-adrenergic response was predominant over the β-adrenergic one in adult rat hepatocytes, when the responses were measured as the agonist-induced generations of Ins(1,4,5)P3 and cyclic AMP, respectively. During primary culture of the adult rat hepatocytes, the β-adrenergic response developed rapidly, whereas the α1-response decreased gradually. Such receptor-subtype switching did not occur unless the cells were cultured under conditions favourable for cell growth, i.e. at low cell density (104 cells/cm2). The switching was prevented progressively as the cell culture density was increased up to 20-fold or the low-density culture was achieved by addition of increasing amounts of liver plasma membranes. The gradual decrease in α1-response was accounted for by a concurrent decrease in the receptor site density, whereas rapid development of the β-response definitely preceded the increase in β-ligand binding sites during the culture. This rapid development of the β-response reflected enhanced coupling of the receptor to G-protein during the early stage of culture, as evidenced by the progressively developed ability of GTP to lower the affinity of β-agonist binding to membranes prepared from these short-time-cultured hepatocytes.