Effect of 4‐aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation.

Abstract

1. 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 mM. At 10 mM, it induced spontaneous release of NA which was insensitive to calcium. 3. Insignificant outputs obtained at 5 Hz in 0.1 and 0.3 mM calcium‐Krebs solution were markedly enhanced by 4‐AP. 4‐AP enhanced release at all calcium concentrations up to 5 mM, but maximum output was obtained at 2.5 mM. 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.