Studies on Responsiveness of Hepatoma Cells to Catecholamines III. Difference between the Receptor-Adenylate Cyclase Regulating Systems in AH130 Cells and Cultured Normal Rat Liver Cells

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Abstract
The responsiveness to three .beta.-adrenergic agonists, isoproterenol (IPN), epinephrine (Epi) and norepinephrine (NE) in AH130 cells was examined compared with that in normal rat liver cells which were cultured for 24 hr after collagenase digestion. As regards to the activation of adenylate cyclase in the cell homogenates, the relative affinity of the three agonists was in order of IPN > NE > Epi in AH130 cells and IPN > Epi > NE in cultured normal liver cells. While the efficacies of the three agonists were similar in cultured liver cells, those of NE and Epi were markedly lower than that of IPN in AH130 cells and were increased to the similar level of IPN by pretreatment with phentolamine, but not with prazosin. Clonidine inhibited the activation of adenylate cyclase by IPN in AH130 cells. When cells were preincubated with islet-activating protein (IAP), the activity of adenylate cyclase in the presence or absence of agonist in both cell lines increased. In IAP-treated AH130 cells, the efficacies of NE and Epi became close to that of IPN. Adenylate cyclase in IAP-treated AH130 cells was activated by GTP in a dose-dependent manner, but that in IAP-treated cultured liver cells was not. In the presence of IPN, biphasic (activatory and inhibitory) effects of GTP on the cyclase were observed, and the inhibitory phase was eliminated by the IAP-treatment in both cell lines. From these results, it is suggested that .beta.-adrenoceptors in AH130 cells have similar properties to .beta.1-receptors and that adenylate cyclase was restricted by inhibitory guanine nucleotide regulatory protein which closely interacts with an inhibitory receptor such as the .alpha.2-adrenoceptor in AH130 cells and interacts with a stimulatory receptor such as the .beta.2-adrenoceptor in cultured normal rat liver cells.