Noradrenergic presynaptic nerve

Dextroamphetamine is a powerful stimulant of the nervous system that manifests its effects by releasing dopamine and norepinephrine from presynaptic nerve endings, thus stimulating central dopaminergic and noradrenergic receptors. In certain doses it strengthens the excitatory process in the CNS, reduces fatigue, elevates mood and the capacity to work, reduces the need for sleep, and decreases appetite. 

FIGURE 12—5. Here, /-amphetamine is releasing norepinephrine from presynaptic noradrenergic neurons. It also does this from dopamine neurons, just as shown for (/-amphetamine in Figure 12—3. When /-amphetamine binds to ther-presynaptic norepinephrine transporter on the norepinephrine presynaptic nerve terminal, it not only blocks norepinephrine reuptake but actually causes norepinephrine release. Thus, /-amphetamine releases both norepinephrine and dopamine, whereas (/-amphetamine is selective for dopamine. Since norepinephrine and dopamine can have different if related cognitive functions in different patients, then d- and /-amphetamine can have different cognitive effects as well. 

Reuptake inhibitor An indirectly acting drug that increases the activity of transmitters in the synapse by inhibiting their reuptake into the presynaptic nerve ending. May act selectively on noradrenergic, serotonergic, or both types of nerve endings... 

Nonpeptide receptors Adenosine Aj Human cDNA Cardiac arrhythmia, asthma, myocardial ischemia, obesity, pain, renal disease, sleep apnea, stroke, cancer, inflammation, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Bradycardia, lipolysis inhibition, reduction of glomerular filtration and natriuresis, tubero-glomerular feedback, antinociception, renal vasodilatation-constriction, reduction of central cholinergic and noradrenergic nerve activity, presynaptic inhibition of excitatory neuro transmission... 

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. 

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). 

CNS Autoreceotors for Norepinephrine (NE) - Though the concept of autoinhibition of NE release is not universally accepted,the consensus is that release of NE from sympathetic nerves is modulated through inhibitory a2 autoreceptors. By contrast, somadendritic a2-adreno-ceptors of central noradrenergic neurons inhibit firing.Release of H-amezinium from rat cortical noradrenergic axons has been advanced as a model for the study of the a2-autoreceptor hypothesis. There are a number of mechanisms possible for the link between presynaptic a2 adrenoceptor activation and transmitter release, in which a pivotal role for Ca2+ has been established.3.8 (tore recent data implicates inhibition of adenylate cyclase with receptor activation and subsequent attenuation of transmitter release. 

---