C-type natriuretic peptide modulates glutamate receptors on cultured rat retinal amacrine cells

Abstract

C-type natriuretic peptide, widely distributed in the CNS, may work as a neuromodulator. In this work, we investigated modulation by C-type natriuretic peptide of functional properties of glutamate receptors in rat retinal GABAergic amacrine cells in culture. Immunocytochemical data revealed that natriuretic peptide receptor-B was strongly expressed on the membrane of cultured GABAergic amacrine cells. By whole cell recording techniques we further identified the glutamate receptor expressed on the GABAergic amacrine cells as an AMPA-preferring subtype. Incubation with C-type natriuretic peptide suppressed the AMPA receptor-mediated current of these cells in a dose-dependent manner by decreasing the efficacy and apparent affinity for glutamate. The effect of C-type natriuretic peptide was reversed by HS-142-1, a guanylyl cyclase-coupled natriuretic peptide receptor-A/B antagonist. Meanwhile, the selective natriuretic peptide receptor-C agonist cANF did not change the glutamate current. In conjunction with the immunocytochemical data, these results suggest that the C-type natriuretic peptide effect may be mediated by natriuretic peptide receptor-B. Furthermore, incubation of retinal cultures in the C-type natriuretic peptide-containing medium elevated cGMP immunoreactivity in the GABAergic amacrine cells, and the C-type natriuretic peptide effect on the glutamate current was mimicked by application of 8-Br-cGMP. It is therefore concluded that C-type natriuretic peptide may modulate the glutamate current by increasing the intracellular concentration of cGMP in these cells via activation of natriuretic peptide receptor-B.