Cholera Toxin ACTH-Unresp can ADP-Ribosylate Gs as well as Gi in onsive Human Adrenocortical Cancer

It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has 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 cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 40 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADPribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.