Adrenergic antagonists, and a possible link between the increase in cyclic adenosine 3′,5′‐monophosphate and DNA synthesis during liver regeneration

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Abstract
The cyclic‐AMP concentration in the liver remnant after 70% hepatectomy increases in a biphasic manner with peak values at 3 and 12 hours, and DNA synthesis begins at 18 hours. Propranolol (dl) injected at 30 minutes after surgery stopped the first wave of cyclic‐AMP accumulation, but did not affect the second accumulation or the initiation of DNA synthesis. However, dl, propranolol injected at eight hours equally delayed (by 6 to 8 hours) the second wave of cyclic‐AMP accumulation and the initiation of DNA synthesis. Propranolol (dl) did not affect DNA replication per se, since it was totally ineffective after the second wave of cyclic‐AMP accumulation had passed and DNA synthesis had been initiated. Propranolol (dl) action was not due to a blockade of β‐adrenergic receptors, since its d or l isomers were separately without effect, as were unrelated β‐adrenergic blockers (Kü 1313 and M&B 17‐803A).On the other hand, an activation of α‐adrenergic receptors may be involved in the induction of hepatocyte proliferation, since α‐adrenergic antagonists, such as phenoxybenzamine and phentolamine, both delayed and considerably reduced the second wave of cyclic‐AMP accumulation and the subsequent initiation of DNA synthesis. It is concluded that the second wave of cyclic‐AMP accumulation is somehow associated with the initiation of DNA synthesis.

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