Feedback control of noradrenaline release as a function of noradrenaline concentration in the synaptic cleft in cortical slices of the rat.

Cortical slices incubated with [3H]noradrenaline (NA) were used to study quantitatively the infelucne of the NA concentration in the synaptic cleft on electrically induced release of [3H]NA from adrenergic nerve terminals. Stimulation-induced [3H]-overflow was regarded to be proportional to the NA concentration in the synaptic cleft. High concentrations of piperoxan or clonidine were used to block, or maximally stimulate, respectively, the presynaptic alpha-receptors and thus to eliminate feedback control. These two extreme conditions were thought to delineate maximal feedback range. With alpha-receptors not artifically manipulated, [3H]overflow increased with stimulus intensity, yet not in proportion to the [3H]-overflow when the presynaptic alpha-receptors were blocked, demonstrating increasing feedback inhibition with increasing NA concentrations in the synaptic cleft. Feedback inhibition of NA release was shown to depend in an exponential fashion on NA concentration in the synaptic cleft. The slope of the regression line indicated that maximal inhibition of NA release occurred with NA concentrations in the synaptic cleft 65,000--700,000 times higher than threshold concentration. Data from experiments with different stimulus rates also supported the notion of feedback control of NA release.