Slopes of dose-response curves to norepinephrine in isolated strips of the cat's spleen

In isolated strips of the spleen capsule, the shifts to the right in dose-response curves to norepinephrine obtained in the presence of phentolamine were accompanied by an increase in the slope of the dose-response curve. This phenomenon was observed both in normal and in reserpine-pretreated tissues. There was a correlation between the potency of norepinephrine and the slope of the dose-response curve: the lower the potency, the higher the slope of the curve. When neuronal uptake of norepinephrine was inhibited by cocaine or abolished by denervation, no increase in slopes was observed in the presence of phentolamine and the shifts in the dose-response curves to norepinephrine were parallel. Studies on uptake and retention of 3H-norepinephrine in isolated strips of the spleen capsule confirmed the saturable nature of this process. There was a good correlation between the range of oncentrations of norepinephrine at which saturation of neuronal uptake occurred and the concentrations corresponding to the ED 20 of the curves in which there was an increase in the slopes. The results obtained are compatible with the view that the increase in the slopes of the dose-response curves is of presynaptic origin and related to the saturation of neuronal uptake of the amine. The latter leads to the loss of the linear relationship between the concentration of norepinephrine in the organ bath and in the vacinity of the receptors which results in steeper dose-response curves.