title: Membrane receptor function and the loss of glucagon-stimulated adenylate cyclase activity in hepatomas.
abstract: Plasma membranes were prepared from homogenates of two well differentiated hepatomas (Morris rat 7787 and Dalton mouse 9815), two poorly differentiated hepatomas (Morris rat 7288-C and Dalton mouse 129), and normal liver. Adenylate cyclase activity and [125I]iodoglucagon binding were measured in the plasma membrane preparations over a wide range of glucagon concentrations. Nether glucagon-stimulated adenylate cyclase activity nor [125I]iodoglucagon binding could be detected in the poorly differentiated hepatomas. Fluoride and epinephrine stimulated adenylate cyclase activity in all hepatomas. Maximum activity of glucagon-stimulated adenylate cyclase and maximum binding of glucagon in the wall differentiated hepatomas were less than those of normal liver. Plasma membranes from liver and hepatomas were solubilized with Lubrol-PX and, after reducing the concentration of detergent, were incubated with [125I]iodoglucagon and then chromatographed on a column of Bio-Gel A 1,5 m. Two peaks containing both protein and [125I]iodoglucagon were found for normal liver but not for the poorly differentiated hepatomas. Fractions from the Bio-Gel column containing the greatest concentration of protein were also subjected to a binding microassay. Material from the poorly differentiated tumors did not bind glucagon in this system, whereas the solubilized normal liver membranes bound up to 1.4 pmol [125I]iodoglucagon/mg protein. This indicates that there is no detectable glucagon receptor in these undifferentiated tumors.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008297:Male; D051379:Mice; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D012995:Solubility
chemical_list: D011956:Receptors, Cell Surface; D005934:Glucagon; D000262:Adenylyl Cyclases; D005459:Fluorides; D004837:Epinephrine