Effect of nerve stimulation on the noradrenaline content of the spleen

Abstract

Although large amounts of transmitter are known to overflow from the spleen during nerve stimulation, an accompanying depletion of the spleen's noradrenaline content has not hitherto been demonstrated. A method has been developed for measuring changes in the noradrenaline content of the cat's spleen. Control portions of the organ were removed before stimulation and correction was made for the contraction and change in wet weight of the stimulated portion by expressing noradrenaline in terms of the tissue deoxyribonucleic acid (DNA). Transmitter overflowing into the venous blood was assayed. Trains of 500 to 9000 stimuli delivered to the splenic nerves at 30/s produced variable changes in noradrenaline/g wet weight, which were dependent on the initial state of distention of the spleens with blood. Calculated in terms of DNA an underlying mean depletion of 8% was observed. A corresponding amount of transmitter overflowed into the venous blood. In similar experiments with phenoxybenzamine, the depletion was nearly four times greater and there was an equivalent increase in the amount of transmitter overflowing. Most of the depletion occurred with the shorter trains of stimuli when the overflow was greatest. Phenoxybenzamine blocks the uptake of noradrenaline by the spleen and the overflow then approximates to the liberation by the nerves. Both the liberation and the vascular and volume responses of the spleen reached their maxima with the shorter trains and then declined with increasing numbers of stimuli, although the action potentials measured in the splenic nerve were maintained throughout 9000 stimuli. Neither synthesis nor degradation of transmitter were considered to be quantitatively important in the duration of these experiments. The results indicate that uptake was proportional to liberation, approximately 70% of the liberated transmitter being rebound in the spleen in an extractable form. About one-third of the noradrenaline in the nerve was readily available for release, and this could rapidly be depleted by nerve stimulation at 30/s.