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

George J. Trachte

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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 of N- nitro-L-arginine methyl ester or an active fragment of the NPR-C receptor administered in permeabilized cells. Further more, 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.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume294
Issue number1
StatePublished - Jul 2000

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