Physiological significance of α-adrenoceptor-mediated negative feedback mechanism regulating noradrenaline release during nerve stimulation

Abstract

NORADRENERGIC nerve endings in the peripheral nervous system are involved in the synthesis, storage, release and uptake of the neurotransmitter. The view that released noradrenaline interacts only with the postsynaptic receptors of the effector cell to elicit the typical response (contraction of a smooth muscle, positive chronotropic and inotropic effects) has been challenged by the proposal that specific receptors might also be present in the outer surface of the membrane of nerve endings^1–5. These presynaptic receptors are of the α-adrenergic type, mediating a negative feedback mechanism regulating noradrenaline release during nerve stimulation^1–5. The noradrenaline thus released, on reaching a threshold concentration in the synaptic gap, activates presynaptic α adrenoceptors triggering a negative feedback mechanism that inhibits further release of the transmitter. In support of this view, it has been reported that activation of presynaptic α adrenoceptors leads to a decrease in transmitter release, while blockade of these receptors results in an increase in noradrenaline release during nerve stimulation⁵. We have now demonstrated that the negative feedback mechanism mediated by presynaptic α adrenoceptors has a physiological role in neurotransmission.