INHIBITION OF ADENYLATE-CYCLASE-COUPLED G-PROTEIN COMPLEX BY OTOTOXIC DIURETICS AND CISPLATINUM IN THE INNER-EAR OF THE GUINEA-PIG

The enzyme adenylate cyclase produces the second messenger cAMP and is located in the mammalian inner ear, predominantly in the stria vascularis and to a lesser extent in the organ of Corti. It is coupled to hormone receptors and regulating G proteins in the outer cell membrane. By means of immunofluorescence in cryostat sections of the guinea pig cochlea, we could demonstrate the G proteins G(s) and G(i), which belong to the adenylate cyclase complex. These proteins had their highest density in the stria vascularis. In membrane preparations of this tissue, the adenylate cyclase complex was inhibited by ototoxic drugs (furosemide, ethacrynic acid and cis-platinum). Stimulation at different sites of the enzyme system showed that the target of these drugs was probably the regulating G protein complex and not the enzyme molecule itself. Inhibition depended on the concentration of the drug and the incubation time.