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(Hypertension. 1999;33:124-129.)
© 1999 American Heart Association, Inc.

Scientific Contributions

C-Type Natriuretic Peptide Attenuates Evoked Dopamine Efflux by Influencing G_o

Satoshi Takida; Barbara J. Elmquist; George J. Trachte

From the Department of Pharmacology, University of Minnesota-Duluth, School of Medicine, Duluth, Minn.

Correspondence to Dr George J. Trachte, Department of Pharmacology, University of Minnesota-Duluth, School of Medicine, 10 University Dr, Duluth, MN 55812. E-mail gtracht1{at}d.umn.edu

Abstract—Natriuretic peptides suppress adrenergic neurotransmission by a mechanism sensitive to pertussis toxin, suggesting that GTP-binding proteins are involved in the response. The major GTP-binding proteins present in the pheochromocytoma (PC12) cells used in this report are G_o and G_i2. We tested the hypothesis that the more abundant GTP-binding protein, G_o, mediates natriuretic peptide effects in PC12 cells by selectively ablating G_o from the cells with antisense oligodeoxynucleotides. The results indicate that a selective ablation of G_o with this technique eliminated C-type natriuretic peptide (CNP) effects and suppressed dopamine efflux evoked by a depolarizing stimulus. However, the activation of guanylyl cyclase (GC) by CNP was sustained after the G_o ablation. Further, N-nitro-L-arginine methyl ester suppressed evoked dopamine efflux equally in the presence and absence of G_o. These results suggest that CNP attenuates evoked catecholamine efflux from PC12 cells by a mechanism requiring G_o but independent of GC activation.

Key Words: neurotransmission • GTP-binding proteins • oligodeoxynucleotides, antisense • pheochromocytoma cells • guanylyl cyclase

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