Release of noradrenaline from cat spleen slices by potassium

1 When cat spleen slices were exposed to a potassium-enriched (140 mM) Krebs solution, 367 +/- 31 ng g-1 5 min-1 of noradrenaline (NA) was released into the bathing medium. 2 Phenylephrine and clonidine (10(-7) to 10(-3) M) did not significantly modify the potassium-evoked NA release; acetylcholine decreased it in a dose-dependent manner. 3 Phenoxybenzamine increased NA release by 50% but phentolamine did not alter it; high concentrations of this drug greatly decreased NA release. Cocaine increased the NA release by about 30%. 4 It is suggested that the failure of sympathomimetic amines to depress, and of alpha-adrenoceptor blocking agents to enhance the release of NA by high potassium concentrations may be related to prolonged depolarization of the nerve terminals, which may desensitize presynaptic alpha-receptors. The fact that the same drugs are able to modify NA release during electrical nerve stimulation may be ascribed to the much shorter periods of depolarization occurring under these conditions.