C-type natriuretic peptide attenuates evoked dopamine efflux by influencing G(0)alpha

Natriuretic peptides suppress adrenergic neurotransmission by a mechanism s ensitive to pertussis toxin, suggesting that GTP-binding proteins are invol ved in the response. The major GTP-binding proteins present in the pheochro mocytoma (PC12) cells used in this report are G(o)alpha and G(i)alpha(2). W e tested the hypothesis that the more abundant GTP-binding protein, G(o)alp ha, mediates natriuretic peptide effects in PC12 cells by selectively ablat ing G(o)alpha from the cells with antisense oligo deoxynucleotides. The res ults indicate that a selective ablation of G(o)alpha with this technique el iminated C-type natriuretic peptide (CNP) effects and suppressed dopamine e fflux evoked by a depolarizing stimulus. However, the activation of guanyly l cyclase (GC) by CNP was sustained after the G(o)alpha ablation. Further, N-omega-nitro-L-arginine methyl ester suppressed evoked dopamine efflux equ ally in the presence and absence of G(o)alpha. These results suggest that C NP attenuates evoked catecholamine efflux from PC12 cells by a mechanism re quiring Go(alpha) but independent of GC activation.