Noradrenergic nerve terminal

Noradrenaline release might also be modulated by receptors on noradrenergic nerve terminals that are activated by other neurotransmitters ( heteroceptors ). Unfortunately, most studies of this type of modulation have been carried out in tissue slices and... 

Localisation of specific NT terminals. After its injection a labelled precursor should be taken up and detected in appropriate nerve terminals (and possibly cell bodies) so that the intensity of emission reflects the density of nerve terminals and the innervation. Using this procedure it has been possible to show that very little [ F] fluorodopa is concentrated in the striatum of Parkinsonian patients, compared with normals (Fig. 14.1). Whether the label remains on dopa or is transferred to dopamine will not greatly affect the result since both will label DA neurons although some will occur in noradrenergic nerve terminals. 

The postsynaptic receptors on any given neuron receive information from transmitters released from another neuron. Typically, postsynaptic receptors are located on dendrites or cell bodies of neurons, but may also occur on axons or nerve terminals in the latter case, an axoaxonic synaptic relationship may cause increases or decreases in transmitter release. In contrast, autoreceptors are found on certain neurons and respond to transmitter molecules released from the same neuron. Autoreceptors may be widely distributed on the surface of the neuron. At the nerve terminal, they respond to transmitter molecules released into the synaptic cleft on the cell body, they may respond to transmitter molecules released by dendrites. Functionally, most autoreceptors appear to decrease further transmitter release in a kind of negative feedback loop. Autoreceptors have been identified for all the catecholamines, as well as for several other neurotransmitters. a2-adrenergic receptors are often found on noradrenergic nerve terminals of postganglionic sympathetic nerves, as well as on noradrenergic neurons in the CNS [36], and activation of these receptors decreases further norepinephrine release. Dopamine autoreceptors,... 

Angiotensin II, acting at presynaptic receptors on noradrenergic nerve terminals, potentiates the release of norepinephrine during low-frequency sympathetic nerve stimulation. Aside from its action on the nerve terminals of postganglionic sympathetic neurons, angiotensin II can directly stimulate sympathetic neurons in the central nervous system, in peripheral autonomic ganglia, and at the adrenal medulla. 

Control of transmitter release is not limited to modulation by the transmitter itself. Nerve terminals also carry regulatory receptors that respond to many other substances. Such heteroreceptors may be activated by substances released from other nerve terminals that synapse with the nerve ending. For example, some vagal fibers in the myocardium synapse on sympathetic noradrenergic nerve terminals and inhibit norepinephrine release. Alternatively, the ligands for these receptors may diffuse to the receptors from the blood or from nearby tissues. Some of the transmitters and receptors identified to date are listed in Table 6-4. Presynaptic regulation by a variety of endogenous chemicals probably occurs in all nerve fibers. 

Allgaier C, Daschmann B, Sieverling J, Hertting G (1989) Presynaptic K-opioid receptors on noradrenergic nerve terminals couple to G proteins and interact with the a2-adrenoceptors. J Neurochem 53 1629-1635. 

In addition to being synthesized in the peripheral nervous system, dopamine is synthesized in the corpus striatum and in the mesocortical, mesolimbic, and tuberoinfundibular systems. Norepinephrine is synthesized and stored primarily in sympathetic noradrenergic nerve terminals, as well as in the brain and the adrenal medulla. Epinephrine is synthesized and stored primarily in the adrenal medulla and, to a certain extent, in the hypothalamic nuclei. 

The principle of negative feedback control is also found at the presynaptic level of autonomic function. Important presynaptic feedback inhibitory control mechanisms have been shown to exist at most nerve endings. A well-documented mechanism involves an 2 receptor located on noradrenergic nerve terminals. This receptor is activated by norepinephrine and similar molecules activation diminishes further release of norepinephrine from these nerve endings (Table 6-4). Conversely, a presynaptic Breceptor appears to facilitate the release of norepinephrine. Presynaptic receptors that respond to the transmitter substances released by the nerve ending are called autoreceptors. Autoreceptors are usually inhibitory, but many cholinergic fibers, especially somatic motor fibers, have excitatory nicotinic autoreceptors. 

Allgaier C, Greber R, Hertting G (1991) Studies on the interaction between presynaptic 012-adrenoceptors and adenosine Ai receptors located on noradrenergic nerve terminals. Naunyn-Schmiedberg s Arch Pharmacol 344 187-92... 

ATP is a well-established co-transmitter to noradrenaline in the central (Poelchen et al. 2001) as well as peripheral (von Kugelgen and Starke 1991) nervous system. Therefore, the functions of presynaptic P2X receptors have been investigated in various preparations containing noradrenergic nerve terminals (Cunha and Ribeiro 2000). Early evidence for a stimulation and positive feedback modulation of noradrenaline via presynaptic P2X receptors has been obtained in sympathetic neurons (Boehm 1999). At the neuromuscular junction, ATP stimulated the release of acetylcholine (1994), and this effect was suggested to be mediated by presynaptic P2X7 receptors (Moores et al. 2005). 

CO-beneldopa benserazide levodopa. cocaine (ban, usan] (cocaine hydrochloride (jan, usan)) is an ester of benzoic acid and methylecgonine and the principal alkaloid of Erythroxylum coca and other Erythroxylum spp. (Erythroxylaceae). It is a LOCAL ANAESTHETIC (used topically because of toxicity), and has pronounced indirect-acting SYMPATHOMIMETIC actions by virtue of being an UPTAKE INHIBITOR (interferes with Uj active uptake of noradrenaline into noradrenergic nerve terminals). It is a VASOCONSTRICTOR and can be used as a topical mydriatic and ocular diagnostic agent. It is a powerful CNS stimulant (similar in action to amphetamine), with considerable abuse potential, cocaine hydrochloride cocaine. 

Deprenyl (we used the racemic compound under the code name E-250 in the first series of experiments) proved to be a compound with a peculiar pharmacological spectrum. We described it in our first paper as a new spectrum psychic energizer (Knoll et al. 1965). I selected this compound for further development because I was fascinated by the finding that in contrast to MAO inhibitors, which potentiated the blood pressure increasing effect of amphetamine, a releaser of norepinephrine from their stores in the noradrenergic nerve terminals, E-250 inhibited it (see Fig. 1 in Knoll et al. 1965). Based on this observation we analyzed this peculiar behavior in more detail. As I expected, the studies revealed that deprenyl, in contrast to the known MAO inhibitors, did not potentiate the effect of tyramine but inhibited it. This effect of deprenyl was first demonstrated in a study performed on cats and on the isolated vas deferens of rats. The hope was expressed in this paper that this... 

Those which have activity at noradrenergic nerve terminals, including doxepin, amitriptyline, and desipramine. 

L-dopa is taken into both dopaminergic and noradrenergic nerve terminals, both in the CNS and periphery. Thus, peripheral levels of dopamine and norepinephrine may increase with administration of the drug, resulting in effects on the cardiovascular system, renal blood flow, and skeletal muscle function. 

No. Therapy should not be initiated for at least 2 weeks post removal of MAO inhibitor therapy, because otherwise a hypertensive crisis may result. This effect is largely due to the increase in norepinephrine synthesis produced with L-dopa therapy, due to the uptake of L-dopa by peripheral noradrenergic nerve terminals and subsequent conversion to norepinephrine. 

PP also inhibits tt2-ADR receptors located on serotonergic/noradrenergic nerve terminals. Hence, it also causes a net increase of serotonin (and norepinephrine in specific regions) secretion from the nerve terminals... 

Figure 6-2. Characteristics of transmitter synthesis, storage, release, and termination of action at cholinergic and noradrenergic nerve terminals are shown from the top downward. Circles represent transporters ACh. acetylcholine AChE. acetylcholinesterase ChAT, choline acetate transferase DOPA, dihydroxyphenylalanine NE, norepinephrine TCA, tricyclic antidepressant TH, tyrosine hydroxylase.

X,-Adrenoceptors occur on noradrenergic nerve terminals. Their activation by norepinephrine inhibits adeny lyl cyclase. The consequent fall in cAMP doses Ca channels and diminishes further transmitter release. 

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