INCREASES IN RAT-LIVER CYCLIC-AMP AND GLYCOGEN-PHOSPHORYLASE ACTIVITY CAUSED BY THE HERBICIDE ATRAZINE

The in vivo effects of the triazine herbicide atrazine on rat liver glycogen metabolism was investigated. After administration of atrazine, liver c-AMP was elevated up to threefold, the activity of glycogen phosphorylase increased, the content of glycogen in the liver decreased and the level of blood glucose increased. Cyanuric acid, although not a herbicide but a simple triazine, did alter neither liver c-AMP nor phosphorylase activity. In vitro adenylate cyclase was not activated or inhibited by triazine. However, phosphodiesterase was inhibited non-competitively by the herbicide (0.1-0.4 mM), resembling theophylline in this respect. When atrazine was added to isolated hepatocytes the effect of glucagon-stimulated c-AMP accumulation was potentiated. Thus, atrazine can inhibit phophodiesterase in vitro and in the intact cell. This phophodiesterase inhibition may also occur in vivo and this may lead to the observed effects on glycogen metabolism. However, additional hormonal and/or nervous alterations caused in vivo by the herbicide can not be excluded. No changes in the activities of adenylate cyclase and of phosphodiesterase could be detected in response to in vivo administration of atrazine. However, these negative results may be the consequence of dissociation of the enzyme-atrazine complex during preparation of the liver fractions. © 1979.