Hepatic adenylate cyclase and phosphodiesterase activity during acute ethionine intoxication

Four hours after the administration of ethionine and in the face of an 80-90% depletion of hepatic ATP there is a twofold increase in cAMP. This increase in cAMP is shown not to be effected by a reduction in phosphodiesterase activity. Both the low Km and high Km forms of the enzyme retain their activity. The purification of liver plasma membranes is not affected by ethionine. There is a significant 20% increase in plasma membrane adenylate cyclase activity following acute ethionine intoxication. This was demonstrable using either ATP or 5'-adenylyl-imidodiphosphate as substrates. The plasma membranes, isolated in the presence of Ca2+, have a 20-fold higher basal adenylate cyclase activity then previously reported and are not further stimulated by GTP or NaF. A modified protocol for isolating cAMP from the adenylate cyclase reaction is described.