Abstract

The mechanism of denervation supereensitivity to norepinephrine was tested by a series of parallel experiments on the cat spleen. Uptake was measured as the removal of norepinephrine from a perfusate. Sensitivity was assessed both in the whole spleen, in situ, and in the isolated spleen strip. Tissue norepinephrine was measured in each spleen. A sharp fall in uptake and tissue norepinephrine began about 48 hours after the removal of the left celiac ganglion and reached a minimum about 48 hours later, while a 20-fold increase in sensitivity to norepinephrine occurred over the same time period. Sensitivity was approximately related to the logarithm of uptake. A rational model, developed from simple assumptions about the distribution of drug between bathing fluid and site of action, and about the kinetics of uptake by nerves, is the basis of an equation that predicts the experimental relation between uptake and sensitivity. This strongly argues that reduction in uptake causes the rapidly developing component of denervation supersensitivity to norepinephrine in the cat spleen.