Lack of glucagon receptors in Morris hepatoma 7800.
When compared to normal liver membranes, purified plasma membranes of regenerating liver and Morris hepatomas contain low but variable capacities to bind glucagon. This property is inversely related to the capacity of the isolated hepatocytes to bind to heterologous biomatrix glycoproteins. Since these parameters are characteristic of the proliferative state of the cells, it was important to further study the glucagon receptor protein and stimulation of adenylate cyclase activity. Our results show that 125I-iodinated plasma membranes obtained from normal liver contain three molecular species (117000, 98000, 86000 molecular weight) that can be eluted specifically with glucagon from a sepharose-glucagon affinity column. These proteins contain the putative glucagon receptor since binding of 125I- iodoglucagon is increased 150-fold as compared to unfractionated membranes. Plasma membranes obtained from Morris hepatoma (7800) and liver of chemically hepatectomized rats do not bind glucagon and lack these proteins. After inactivation with N-ethylmaleimide of the adenylate cyclase activity of the normal plasma membranes, they were fused with membrane of the hepatoma. The hybrid membranes showed 60% recovery of glucagon-stimulated cyclase activity. These results suggest that the plasma membranes of the proliferating liver cells do not contain receptor protein but have intact regulatory and catalytic subunits of the adenylate cyclase system.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D005033:Ethylmaleimide / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000032:analysis*; D008115:Liver Regeneration; D008970:Molecular Weight; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D018027:Receptors, Glucagon
D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D005934:Glucagon; D000262:Adenylyl Cyclases; D005033:Ethylmaleimide