Abstract

Experiments with normal nictitating membranes of pithed cats as well as with isolated normal nictitating membranes show that dose-response curves for a variety of sympathomimetic amines are not parallel: slopes of dose-response curves are inversely related to potency of the amines. The same relationship was observed for a given amine when potency was changed experimentally by decentralization (increase in potency) or by phentolamine (decrease in potency). Since this relationship was not observed after either denervation or cocaine, the phenomenon appears to be related to the uptake of sympathomimetic amines by adrenergic nerve endings. A model is proposed to demonstrate the influence of saturation of uptake on the concentration of amines at the receptors of the effector organ. From the model several postulates were made and tested experimentally. The results indicate that saturation of uptake is one of the factors influencing slopes of dose-response curves. Moreover, saturation of uptake influences the magnitude of shifts of dose-response curves to the left (after decentralization) or to the right (after phentolamine). As a result, a competitive antagonist (phentolamine) appears to be less effective in antagonizing l-norepinephrine on the normal than on the denervated nictitating membrane. For an agent which does not seem to be taken up (i.e., acetylcholine), there is equal antagonism by a competitive antagonist (i.e., atropine) in normal and denervated nictitating membranes.