Depletion of natriuretic peptide C receptors eliminates inhibitory effects of C-type natriuretic peptide on evoked neurotransmitter efflux

GJ Trachte - Journal of Pharmacology and Experimental …, 2000 - ASPET
GJ Trachte
Journal of Pharmacology and Experimental Therapeutics, 2000ASPET
Natriuretic peptides suppress evoked catecholamine efflux by a mechanism attributed to
activation of the natriuretic peptide receptor (NPR)-C, but this designation relies on the
absolute specificity of truncated natriuretic peptide analogs for the NPR-C. The NPR-C
involvement in evoked catecholamine efflux was defined better in this study by selectively
ablating the NPR-C in pheochromocytoma cells with antisense oligodeoxynucleotides. This
treatment suppressed NPR-C levels by 52±4% relative to missense treatment. The reduction …
Natriuretic peptides suppress evoked catecholamine efflux by a mechanism attributed to activation of the natriuretic peptide receptor (NPR)-C, but this designation relies on the absolute specificity of truncated natriuretic peptide analogs for the NPR-C. The NPR-C involvement in evoked catecholamine efflux was defined better in this study by selectively ablating the NPR-C in pheochromocytoma cells with antisense oligodeoxynucleotides. This treatment suppressed NPR-C levels by 52 ± 4% relative to missense treatment. The reduction of NPR-C levels suppressed evoked catecholamine efflux 33 ± 6% and eliminated the effect of C-type natriuretic peptide to suppress evoked catecholamine efflux. The native peptide, C-type natriuretic peptide, reduced evoked catecholamine efflux 39 ± 3% in cells with a normal complement of NPR-C. The NPR-C reduction failed to alter neuromodulatory effects ofN-nitro-l-arginine methyl ester or an active fragment of the NPR-C receptor administered in permeabilized cells. Furthermore, the NPR-C reduction did not prevent guanylyl cyclase activation in response to C-type natriuretic peptide. These latter experiments indicate that the antisense treatment resulted in a specific suppression of the NPR-C and did not affect alternative neuromodulatory pathways or guanylyl cyclase receptors. The novel aspects of this study include both the inhibitory effect of NPR-C reduction on basal-evoked neurotransmitter efflux and the ablation of natriuretic peptide effects on neurotransmitter efflux by NPR-C reduction. The results are consistent with the notion of a key signal-transducing role of the NPR-C in mediating inhibitory effects of natriuretic peptides on neurotransmitter efflux.
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