The signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea

Abstract

Dopamine released from lateral efferent fibers modulates the activity of the auditory nerve, but the signaling mechanism by which this is mediated is not known. The present study investigated the signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea. D1 receptor immunolabeling was localized to the spiral ganglia neurons and at the base of the inner hair cells. Western immunoblotting on whole cochlear preparations revealed positive bands for the D1 receptor and for dopamine and the cyclic AMP-regulated phosphoprotein. The amplitude of the compound action potential was enhanced in the presence of the D1 receptor agonist, SKF 38393, an effect that was abolished by H89, a protein kinase A inhibitor. Conversely, SKF 83566, a D1 receptor antagonist decreased the amplitude of compound action potential, while forskolin, a protein kinase A activator prevented this effect. Furthermore, it was found that the level of glutamate receptor 1 phosphorylation at the protein kinase A site (Ser845) was increased by the D1 agonist, but decreased by D1 antagonist. Our results provide evidence that the D1 receptor is localized in the spiral ganglion neurons as well as the nerve endings under the inner hair cells and they can modulate auditory nerve function. One signal transduction pathway of D1 receptor in the auditory nerve is via protein kinase A-mediated glutamate receptor 1 phosphorylation.