Regeneration of the liver after carbon tetrachloride. Differences in adenylate cyclase and pancreatic hormone receptors.

Plasma membranes were prepared from the liver of rats intoxicated with a single oral dose of carbon tetrachloride.The plasma levels of glucagon and a-fetoprotein increased significantly whereas those of insulin, triiodothyronine, and thyroxine were clearly below normal values.The number of binding sites for insulin and glucagon measured on liver plasma membranes were inversely related to their plasma levels; the insulin binding sites increased 300% over control and glucagon receptors fell drastically.The receptor affinity for both hormones was not altered.These changes in hormone levels and receptors were similar to the changes observed previously in the regenerating liver after partial hepatectomy in adult rat or in fetal liver.The increased number of insulin receptors in regenerating liver either following CCL, or partial hepatectomy coincided in time with the increase of a-fetoprotein; the increased levels of this protein and the increase in number of receptors for insulin and the return to control values of receptors for glucagon was suppressed with cycloheximide and with mitomycin C.These results suggest that the increased number of insulin receptors requires protein synthesis and may not be due to unmasking of hidden sites.The adenylate cyclase response to glucagon was diminished to a greater extent than that to fluoride and was due to the deficiency in the binding of this hormone.The tissue levels of CAMP showed peaks at 6,20, and 48 h after CCL,; the 6and 20-h peaks were not inhibited by propranolol, and the 48-h peak occurred when the adenylate cyclase response to glucagon was at its lowest levels and was suppressed by the 8-adrenergic agent.These studies can be interpreted to mean that liver receptors for pancreatic hormones change differently and are synthesized during liver regeneration after CCL.