C-Type Natriuretic Peptide Attenuates Evoked Dopamine Efflux by Influencing G^o alpha

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 alpha and Gⁱ alpha². We tested the hypothesis that the more abundant GTP-binding protein, G^o alpha, mediates natriuretic peptide effects in PC12 cells by selectively ablating G^o alpha from the cells with antisense oligodeoxynucleotides. The results indicate that a selective ablation of G^o alpha 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 alpha ablation. Further, N^{omega-nitro-L-arginine} methyl ester suppressed evoked dopamine efflux equally in the presence and absence of G^o alpha. These results suggest that CNP attenuates evoked catecholamine efflux from PC12 cells by a mechanism requiring G^o alpha but independent of GC activation. (Hypertension. 1999;33:124-129.).