The cyclic-AMP concentration in the liver remnant after 70% hepatectomy increases i n a biphasic manner with peak values at 3 and 12 hours, and DNA synthesis begins at 18 hours. Propranolol (dt) 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, d l , 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 (cll) 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 ( d l ) action was not due to a blockade of p-adrenergic receptors, since its d or 1 isomers were separately without effect, as were unrelated P-adrenergic blockers (KO 1313 and M&B 17-803A).On the other hand, an activation of a-adrenergic receptors may be involved in the induction of hepatocyte proliferation, since a-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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