Modification of the evoked release of noradrenaline from the perfused cat spleen by various ions and agents.

1. Cat spleens were perfused with Krebs-bicarbonate solution at a rate of about 7 ml./min at 33-35 degrees C. Noradrenaline release after splenic nerve stimulation at 10 or 30 Hz was measured. Effects of various ions and drugs on noradrenaline release were determined.2. Perfusion of phenoxybenzamine- and [(3)H]noradrenaline-treated spleens with 1, 2.5 and 5 mM cobalt or nickel-2 Krebs solution markedly reduced the release of noradrenaline by nerve stimulation. Lanthanum was the most potent inhibitor of noradrenaline release. Increasing the calcium concentration or adding tetraethylammonium chloride (TEA) partially counteracted the inhibitory effects of cobalt on release. Cobalt did not inhibit release induced by tyramine.3. Calcium did not cause spontaneous release of noradrenaline either when high concentrations were injected directly into the spleen or after first perfusing the spleen with calcium-free medium.4. Carbachol, protoveratrine and high potassium inhibit, whereas TEA, barium and rubidium enhance, the evoked release of noradrenaline.5. The relation of noradrenaline release to influx of calcium ions and its modification by various agents has been discussed.