Mechanism of inhibition of catecholamine release from adrenal medulla by diphenylhydantoin and by low concentration of ouabain (10(-10) M).

Catecholamine (CA) release was studied in rat adrenal incubated in vitro. Inhibition of (Na + K)-ATPase either by omission of K+ from the incubation medium or by addition of a high concentration of ouabain (10(-3) M) caused increased release of CA from the adrenal. Diphenylhydantoin (DPH) (10(-5) M) inhibited the spontaneous as well as the acetylcholine (10(-4) M)-induced release of CA. However, in K+-free medium or in the presence of 10(-3) M ouabain, DPH had no significant effect on CA release. A low concentration of ouabain (10(-10) M) caused a significant inhibition of spontaneous and of acetylcholine-induced release of CA. In a K+-free medium ouabain (10(-10) M) had no effect on CA release. DPH (10(-5) M) and a low concentration of ouabain (10(-10) M) caused a significant activation of (Na + K)-ATPase in a membrane fraction of the adrenal medulla. It is suggested that DPH and low ouabain concentrations inhibit CA release from the adrenal by activation of the sodium pump. The possible mechanism involved is discussed.