LOCALIZATION OF SOLUBLE GUANYLATE-CYCLASE ACTIVITY IN THE GUINEA-PIG COCHLEA SUGGESTS INVOLVEMENT IN REGULATION OF BLOOD-FLOW AND SUPPORTING CELL PHYSIOLOGY

Although the nitric oxide/cGMP pathway has many important roles in bio logy, studies of this system in the mammalian cochlea have focused on the first enzyme in the pathway, nitric oxide synthase (NOS). However, characterization of the NO receptor, soluble guanylate cyclase (sGC), is crucial to determine the cells targeted by NO and to develop ratio nal hypotheses of the function of this pathway in auditory processing. In this study we characterized guinea pig cochlear sGC by determining its enzymatic activity and cellular localization. In cytosolic fracti ons of auditory nerve, lateral wall tissues, and cochlear neuroepithel ium, addition of NO donors resulted in three-to 15-fold increases in c GMP formation. NO-stimulated sGC activity was not detected in particul ate fractions. We also localized cochlear sGC activity through immunoc ytochemical detection of NO-stimulated cGMP. sGC activity was detected in Hensen's and Deiters' cells of the organ of Corti, as well as in v ascular pericytes surrounding small capillaries in the lateral wall ti ssues and sensory neuroepithelium. sGC activity was not observed in se nsory celis. Using NADPH-diaphorase histochemistry, NOS was localized to pillar cells and nerve fibers underlying hair cells. These results indicate that the NO/cGMP pathway may influence diverse elements of th e auditory system, including cochlear blood flow and supporting cell p hysiology.