SUMMARY1. 4-aminopyridine (4-AP, 1 mM) increased noradrenaline (NA) output from the perfused cat spleen at 5 Hz by about fivefold. Enhancement of NA release by 4-AP was reversible. Output of NA induced by potassium was not affected.2. NA output was doubled at low concentrations (0.1-0.3 mM) of 4-AP, but maximal effect was obtained at 1-3 m . At 10 m , it induced spontaneous release of NA which was insensitive to calcium. 4. 4-AP at pH 8-5 was more effective in enhancing NA release than at pH 7-4. 5. 4-AP increased the recovery of intra-arterially infused NA from the control 26 to 47 %.6. 4-AP did not affect release of catecholamines (CA) from the perfused cat adrenal gland by acetylcholine (ACh).7. It is suggested that 4-AP inactivates potassium current in sympathetic nerves and prolongs the duration of the action potential, thereby allowing a greater influx of calcium ions into the neurone to enhance release of NA.
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.
SUMMARY1. Experiments were performed on perfused cat adrenal glands to examine the effect of a calcium ionophore A-23187 in the secretion of catecholamines.2. Ionophore (1-10 fM) caused a dose-dependent release of catecholamines and the output was about 100-fold greater at 10 #sm than at 1 jtm.3. Release of catecholamines by the ionophore was dependent on the calcium concentration of the perfusion medium. Omission of calcium blocked the response to the ionophore while excess calcium facilitated it.4. Magnesium antagonized the secretary response to the ionophore. Excess calcium overcame the inhibitory effect of magnesium.5. The ionophore did not modify release of catecholamines by induced splanchnic nerve stimulation.6. The results suggest that the ionophore, like depolarization, introduces calcium into the chromaffin cell to cause release of catecholamines.
The effect of tetraethylammonium (TEA) and barium on release of noradrenaline (NA) from the cat spleen by nerve stimulation or potassium was investigated. 2. In spleens perfused with normal Krebs solution, the NA output at 5 Hz was barely detectable, and the output at 30 Hz was about 5-fold greater than the output at 5 Hz. 3. TEA (1 mM) or barium (2.5 mM) increased NA output at 5 Hz by 5-fold, but did not enhance it at 30 Hz. A maximal effect of TEA was obtained at about 1-3 mM. Enhancement of NA release by TEA was readily reversible. Output of NA induced by high potassium was not affected by TEA or barium. 4. The effect of TEA on release was related to the external calcium concentration. Insignificant outputs obtained at 5 Hz in 0.1 and 0.5 mM calcium-Krebs solutions were markedly increased by TEA, and were 2- and 5-fold greater than the control output at 5 Hz in normal Krebs solution containing 2.5 mM calcium. TEA enhanced release at all calcium concentrations up to 5 mM, but maximum output was still obtained at 2.5 mM. 5. Increasing the potassium concentrations of normal Krebs solution to 10, 15 and 20 mM depressed NA outputs at 5 Hz by 50, 55 and 75% respectively, TEA (1 mM) partially antagonized the inhibitory effect of potassium on release, and in zero potassium-Krebs solution it increased output by about 50% over that obtained in normal Krebs solution. 6. The ratio of NA outputs at 30 and 5 Hz during perfusion with Krebs solution containing TEA was about 0.6, and it approached the normal value as the calcium concentration of the perfusion medium was reduced. TEA facilitated release even at 30 Hz in low-calcium solutions. 7. It is suggested that the enhancement of NA release by TEA and barium is due to the greater influx of calcium ions into the sympathetic nerves during the course of an action potential.
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