On the Mechanism of Nonexocytotic Release of Noradrenaline from Noradrenergic Neurones

Abstract

Postganglionic sympathetic nerve terminals are endowed with two amine carrier systems which are arranged in series (Fig. 1): the vesicular amine carrier present in the membrane of the transmitter storage vesicles and the neuronal amine carrier associated with the axonal membrane of the neurone. Both carrier systems are capable of mediating uphill transport of noradrenaline. The vesicular carrier is driven by the electrochemical H⁺ gradient across the vesicular membrane and brings about countertransport of noradrenaline and H⁺ [1]. By contrast, the neuronal carrier is coupled to the electrochemical Na⁺ gradient across the axonal membrane and mediates cotransport of noradrenaline and Na⁺ [2–4]. Storage vesicles represent what is called a “pump and leak system,” i.e., transport mediated by the vesicular carrier occurs virtually exclusively from “out” to “in,” and noradrenaline can leave the vesicles by simple diffusion only [5]. After leakage, the transmitter is either retaken up by the vesicles or metabolized by monoamine oxidase (MAO) to give dihydroxyphenylglycol (DOPEG), the main presynaptic metabolite of noradrenaline. The drug of choice that selectively blocks the vesicular carrier is reserpine, which also depletes the vesicular noradrenaline stores.