INHIBITORY EFFECTS OF ALLOXAN ON MAMMALIAN ADENYL CYCLASE

The reported antagonism by caffeine of the diabetogenic effect of alloxan prompted examination of a possible action of alloxan on adenyl cyclase. The effects of alloxan on rat liven, heart, kidney and brain and hamster islet cell adenoma adenyl cyclase were studied in in vitro. An assay based on chromatographic isolation of C 14 -cycic 39, 59-adenosine monophosphate was used. Alloxan was found to inhibit adenyl cyclase selectively, reversibly and, in part, competitively. Alloxan, in a concentration of 10 -3 M, produced about 80% inhibition in all tissues examined. In view of the role of adenyl cyclase in the regulation of insulin secretion, it is felt that the inhibition of this en zyme by alloxan might be related to the molecular mechanism of action of this drug in vivo.