Nitric oxide does not mediate promotion of cellular potassium release by phenolphthalein in COS-7 cells.

1. It has been proposed that phenolphthalein exerts its laxative effect via an intracellular cascade that begins with the activation of nitric oxide synthase (NOS) and ends with an inhibition of NaCl and water reabsorption from the colon. Phenolphthalein also promotes the release of potassium from cells, but it is not known how this is related to its effect on sodium and water uptake. 2. An established in vitro system was used to examine the role of nitric oxide (NO) in phenolphthalein-induced release of (86)Rb(+) from COS-7 cells. 3. Sodium nitroprusside, an NOS-independent NO source, was unable to mimic the effects of phenolphthalein and N(G)-nitro-L-arginine methyl ester, an NOS inhibitor, was unable to block the effect of phenolphthalein. 4. It is concluded that NO generation is not required for phenolphthalein-stimulated potassium release. It is proposed that the effect of phenolphthalein on cellular potassium release is mechanistically distinct from the effect on NaCl and water uptake by colonocytes.