Evidence that noradrenergic transmitter release is regulated by presynaptic receptors

A review is provided of the evidence in support of the existence of prejunctional alpha adrenoceptors on noradrenergic nerve terminals as well as the evidence for their physiological importance. The use of alpha-adrenoceptor agonists and antagonists has provided convincing data in support of the presynaptic receptor hypothesis. Moreover, there is ample evidence for the location of alpha adrenoceptors on nerve terminals. This evidence has often been forgotten in arguments opposing the presynaptic alpha-adrenoceptor hypothesis. The precise physiological role of presynaptic alpha adrenoceptors is still an open question, but there is support from a wide range of experiments in favor of a physiological role. Although it is not known which of these functions is most important, presynaptic alpha adrenoceptors may: regulate the pulse-to-pulse regulation of norepinephrine release during nerve stimulation, prevent noise, and protect the neuroeffector cell from excessive activation by transmitter during periods of rest or as physiological antagonists to the facilitation of transmitter release. In summary, evidence reviewed here strongly supports the existence of presynaptic alpha adrenoceptors. These receptors are clearly important pharmacologically and may play a physiological role in noradrenergic transmission. The exact physiological function must await further experimentation.