2',3'-Dialdehyde of GTP blocks regulatory functions of adenylate cyclase NS protein.

Preincubation of bovine caudate nucleus membranes with the 2',3'-dialdehyde of GTP (oGTP) reduces adenylate cyclase activation by guanylyl imidodiphosphate (GppNHp) in a time-dependent fashion. A slower rate of inhibition is observed if membranes are treated with both GTP and oGTP. The efficacy of oGTP action is enhanced by raising the Mg2+ concentration. Reduction of adenylate cyclase sensitivity to GppNHp is followed by an irreversible decrease of enzyme stimulation by forskolin. Addition of a Lubrol soluble preparation from guinea pig lung membranes to oGTP-treated caudate nucleus membranes causes restoration of the adenylate cyclase sensitivity to GppNHp. These data suggest that oGTP blocks the GTP-binding site of the adenylate cyclase system localized on the Ns protein. Such modification leads to the elimination of the Ns-mediated regulation of the enzyme.