Release of noradrenaline by splenic nerve stimulation and its dependence on calcium

Abstract

Cat spleens were perfused with Krebs bicarbonate solution using a constant flow pump. The amount of noradrenaline [norepinephrine] released during splenic nerve stimulation was measured at various frequencies. The dependence of norepinephrine release on the ionic composition of perfusion medium was also determined. The effect of frequency of stimulation on the output of norepinephrine was studied in both normal and phenoxybenzamine treated cats. In normal cats, the output was 0.33 ng/stimulus at 10/sec. whereas at 30/sec, it was 1.21 ng/stimulus. In phenoxybenzamine-treated cats, the maximum output of norepinephrine of 4 ng/stimulus was obtained at 5 or 10/sec. Higher or lower frequencies of stimulation produced lower output. In both normal and phenoxybenzamine treated cats, removal of Ca from the perfusing medium nearly abolished the release of norepinephrine in response to nerve stimulation; replacement of Ca restored the norepinephrine release. The norepinephrine output/stimulus was linearly related to the log of the external Ca concentration. Increasing the concentration of Mg to (10-20 m[image]) reduced the norepinephrine output. This depressant effect of Mg was partially antagonized by increasing the Ca concentration of the perfusion solution. Divalent alkali metal earths such as Ba and Sr could substitute for Ca. Ba substitution nearly doubled the norepinephrine output/stimulus and increased the pressor activity of the samples taken just before nerve stimulation. Removal of K from the perfusion fluid, or lowering the Na concentration to 50 m[image], had little effect on the release of norepinephrine. Lowering the Na concentration to 37.5 m[image] or less usually abolished the norepinephrine output; this effect is attributed to blockade of nerve conduction. Depolarization of post-ganglionic sympathetic nerve terminals may increase the influx of Ca ions, which in turn leads to the release of norepinephrine from the nerve terminals.