Expression of membrane-bound and cytosolic guanylyl cyclases in the rat inner ear

Membrane-bound guanylyl cyclases (GCs) are peptide hormone receptors wherea s the cytosolic isoforms are receptors for nitric oxide. In the inner ear, the membrane-bound GCs may be involved in the regulation of fluid homeostas is and the cytosolic forms possibly play a role in signal processing and re gulation of local blood flow. In this comprehensive study, we examined, qua litatively and quantitatively, the transcription pattern of all known GC is oforms in the inner ear from rat by RT-PCR. The tissues used were endolymph atic sac, stria vascularis, organ of Corti, organ of Corti outer hair cells , cochlear nerve, Reissner's membrane, vestibular dark cells, and vestibula r sensory cells. We show that multiple particulate (GC-A, GC-B, GC-D, GC-E, GC-F and GC-G) and several subunits of the heterodimeric cytosolic GCs (al pha 1, alpha 2, beta 1 and beta 2) are expressed, albeit at highly differen t levels. GC-C was not found. GC-A and the soluble subunits al and pi were transcribed ubiquitously. GC-B was present in all tissues except stria vasc ularis, which contained GC-A and traces of GC-E and GC-G. GC-B was by far t he predominant membrane-bound isoform in the organ of Corti (86%), Reissner 's membrane (75%) and the vestibulum (80%). Surprisingly, GC-E, a retinal i soform, was detected in significant amounts in the cochlear nerve (8%) and in the organ of Corti (4%). Although the cytosolic GC is a heterodimer comp osed of an alpha and a beta subunit, the mRNA transcription of these subuni ts was not stoichiometric. Particularly in the vestibulum, the transcriptio n of the pr subunits was at least four-fold higher than of the alpha 1 subu nit. The data are compatible with earlier suggestions that membrane recepto r GCs may be involved in the control of inner ear electrolyte and fluid com position whereas NO-stimulated GC isoforms mainly participate in the regula tion of blood flow and supporting cell physiology. (C) 1999 Elsevier Scienc e B.V. All rights reserved.