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>Stimulatory and inhibitory effects of catecholamines on DNA synthesis in primary rat hepatocyte cultures: Role of alpha1‐ and beta‐adrenergic mechanisms
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Stimulatory and inhibitory effects of catecholamines on DNA synthesis in primary rat hepatocyte cultures: Role of alpha1‐ and beta‐adrenergic mechanisms
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机译：Stimulatory and inhibitory effects of catecholamines on DNA synthesis in primary rat hepatocyte cultures: Role of alpha1‐ and beta‐adrenergic mechanisms
AbstractPrevious studies suggest that catecholamines may be involved in the regulation of liver growth. Considerable evidence implicates α1‐adrenergic mechanisms in the initiation of hepatocyte proliferation, while the role of β‐adrenoceptors is less clear. We have examined further the adrenergic regulation of hepatocyte DNA synthesis, using primary monolayer cultures. In hepatocytes that were also treated with epidermal growth factor and insulin, epinephrine or norepinephrine added early after the seeding strongly accelerated the rate of S phase entry. The β‐adrenergic agonist isoproterenol and the α‐adrenergic agonist phenylephrine also stimulated the DNA synthesis, but were less efficient than epinephrine and norepinephrine. Experiments with the α1‐receptor blocker prazosine and the β‐receptor blocker timolol showed that the stimulatory effect of norepinephrine consisted of both an α1‐ and a β‐adrenergic component. The α1‐component was most prominent in terms of maximal response at high concentrations of the agonist, but the β‐component contributed significantly and predominated at low concentrations (<0.1 μM) of norepinephrine. At later stages (about 40 h) of culturing norepi nephrine strongly but reversibly inhibited the cells, acting at a point late in the G1phase. This inhibition was mimicked by isoproterenol and abolished by timolol but was unaffected by prazosine, suggesting a β‐adrenoceptor‐mediated effect. The results confirm the α1‐adrenoceptor‐mediated stimulatory effect, but also show that β‐adrenoceptors may contribute to the growth stimulation by catecholamines. Furthermore, catecholamines, via β‐adrenoceptors and cyclic AMP, inhibit the G1‐S transition, and may thus play a role in the termination
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