Depletion of natriuretic peptide C receptors eliminates inhibitory effects of C-type natriuretic peptide on evoked neurotransmitter efflux.
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. 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.
Trachte
G J
GJ
Department of Pharmacology, University of Minnesota-Duluth, School of Medicine, Duluth, Minnesota 55812, USA. gtracht1@d.umn.edu
D000595:Amino Acid Sequence; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000502:physiology*; D008969:Molecular Sequence Data; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology*
D016376:Oligonucleotides, Antisense; D020098:Natriuretic Peptide, C-Type; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D006152:Cyclic GMP; D011188:Potassium; D004298:Dopamine