Cyclic GMP efflux from liver slices.

Cyclic GMP efflux from liver slices was studied when the intracellular cyclic GMP levels were elevated by incubation with N-methyl-N'-nitro-N-nitrosoguanidine (0.1 mM) and 3-isobutyl-1-methylxanthine (0.25 mM). A probenecid-sensitive and a probenecid-insensitive efflux system for cyclic GMP was found. It is suggested that the former system operates a carrier, which is saturable, the capacity of which is increased by alkylation with N-ethylmaleimide. The rate of net efflux of cyclic GMP increases 20-fold in the temperature interval 18-37 degrees C. Probenecid (0.5 mM) gives 50% inhibition of this system. The probenecid-insensitive cyclic GMP efflux component probably corresponds to passive diffusion. It appears that efflux may be an important complement to cyclic 3':5'-nucleotide phosphodiesterase activity in reducing intracellular cyclic GMP levels.