Presynaptic regulation of the release of catecholamines

Abstract

During norepinephrine release elecited by the arrival of nerve impulses, the neurotransmitter interacts with specific receptors (alpha1-, beta1-, beta2-adrenoceptors) located in the membrane of the postsynaptic cell to trigger the response of the effector organ. Until a few years ago, it was thought that the role of noradrenergic nerve terminals in neurotransmission is concerned exclusively with the synthesis, storage, release, and inactivation of norepinephrine and there were no indications that receptors might also be present in the presynaptic membrane. During the last decade, evidence has accumulated in favour of the view that, in addition to the classical postsynaptic adrenoceptors that mediate the responses of the effector organ, there are also receptors located on the noradrenergic nerve terminals. These presynaptic recptors are involved in the modulation of the calcium-dependent, action-potential-evoked release of norepinephrine in the peripheral as well as in the central nervous system. Presynaptic inhibitory alpha-adrenoceptors are involved in the regulation of the release of norepinephrine through a negative feedback mechanism mediated by the neuron's own transmitter. Alpha-Adrenoceptor agonists inhibit the release of norepinephrine during nerve stimulation, while alpha-adrenoceptor blocking agents enhance the stimulation-evoked release of the neurotransmitter. These results have been obtained both i vitro and in vivo. There are pharmacological differences between the postsynaptic alpha-adrenoceptors that mediate the response of the effector organ and the presynaptic inhibitory alpha-adrenoceptors that modulate the release of norepinephrine during nerve stimulation. The subclassification of alpha-adrenoceptors into alpha1- and alpha2-types is bases on differences in relative affinities for a range of alpha-adrenoceptor agoinst and antagonist durgs. The term alpha1-adrenceptor is used for a receptor that is preferentially stimulated by phenylephrine and blocked by prazosin, whereas alpha2-adrenoceptor is reserved for those preferentially stimulated by guanabenz or clonidine and blocked by rauwolscine or yohimbine. The presynaptic inhibitory alpha-adrenoceptors in the peripheral and in the central nervous system have the pharmacological characteristics of the alpha2-adrenoceptors. Presynaptic inhibiotry autoreceptors appear to be involved in the modulation of the release of dopamine and of epinephrine in the central nervous system. A short negative feedback mechanism similar to that for norepinephrine appears to regulate the stimulation-evoked release of dopamine and epinephrine in central neurons. In addition to presynaptic autoreceptors through which the transmitter can modulate its own release, a real mosaic of receptors in present on noradrenergic nerve endings...