CHOLERA-TOXIN CAN ADP-RIBOSYLATE GS AS WELL AS GI IN ACTH-UNRESPONSIVE HUMAN ADRENOCORTICAL CANCER

It is well known that cholera toxin (CT) stimulates ADP-ribosylation o f Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein h as its own action in the regulation of adenylate cyclase. A human non- functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cy clase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 40 kDa protein of the plasma membrane of the cancer tissue while CT an d PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tis sue, respectively. Immunoblotting analysis of the cancer tissue demons trated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT cou ld ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested th at CT can activate the ADP-ribosylation of Gs and also Gi in a human a drenocortical cancer tissue, partly resulting in abnormal regulation o f adenylate cyclase which may be crossly related to ACTH-unresponsiven ess.