Catecholaminergic neurons

In this lecture we will be concerned by exocytosis of neurotransmitters by chromaffin cells. These cells, located above kidneys, produce the adrenaline burst which induces fast body reactions they are used in neurosciences as standard models for the study of exocytosis by catecholaminergic neurons. Prior to exocytosis, adrenaline is contained at highly concentrated solutions into a polyelectrolyte gel matrix packed into small vesicles present in the cell cytoplasm and brought by the cytoskeleton near the cell outer membrane. Stimulation of the cell by divalent ions induces the fusion of the vesicles membrane with that of the cell and hence the release of the intravesicular content into the outer-cytoplasmic region. 

Fillenz, M (1993) Short-term control of transmitter synthesis in central catecholaminergic neurones. Prog. Biophys. Molec. Biol. 60 29-46. 

Hydroxydopamine (6-OHDA) is a neurotoxin that destroys catecholaminergic neurons in the brain. This toxicity is believed to be related to the production of ROS by the neurotoxin. Rats were fed chronically with vitamin E and then challenged with 6-OHDA. The usual depletion of SOD and reduced glutathione (GSH) in most brain regions was attenuated by the vitamin E pretreatment. The authors attributed this success to scavenging by the augmented brain levels of vitamin E (Perumal et al., 1992). 

Akaoka H., Roussel B., Lin J. S., Chouvet G., Jouvet M. (1991). Effect of modafinil and amphetamine on the rat catecholaminergic neuron activity. Neurosci Lett. 123, 20-2. 

AADC is present not only in serotonergic neurons but also in catecholaminergic neurons, where it converts 3,4-dihydroxyphenylalanine (DOPA) to dopamine (see Ch. 12). However, different pH optima or concentrations of substrate or cofactor are required for optimum activity of the enzyme in brain homogenates when using either 5-HTP or DOPA as the substrate. cDNAs encoding AADC... 

Tyrosine hydroxylase is present in neurons in the CNS and PNS that synthesize catecholamines. The enzyme is also present at high concentrations in cells that are devel-opmentally related to catecholaminergic neurons, such as... 

Large amounts of iron are sequestered in substantia nigra and in locus coerulus as a neuromelanin-iron complex in dopaminergic neurons particularly in PD. Neuromelanin, a granular dark brown pigment, is produced in catecholaminergic neurons of the SN and... 

Petrucelli, L., et al.. Parkin protects against the toxicity associated with mutant alpha-synuclein proteasome dysfunction selectively affects catecholaminergic neurons. Neuron,... 

Haglund L, Kohler C, Haaparanta T, Goldstein M, Gustafsson JA. 1984. Presence of NADPH-cytochrome P450 reductase in central catecholaminergic neurones. Nature 307 ... 

Neurotoxins produced by the body. Some normal body constituents are neurotoxic in excess. These incluse quinolinic acid (Fig. 25-11),889 3-hydroxykynurenine (Fig. 25-11 p. 1444),890 and homocysteine.891 Elevated levels of homocysteine are also associated with vascular disease and stroke (Chapter 24). 3-Hydroxykynurenine is a precursor to ommochrome pigments of insects and an intermediate in conversion of tryptophan into the nicotinamide ring of NAD in humans (Fig. 25-11). 6-Hydroxydopamine (Fig. 30-26), which may be formed in the body, is severely toxic to catecholaminergic neurons.892... 

However, receptor autoradiography and in vitro studies have suggested that H3 receptors are located on other aminergic neurons in the brain. Since amines such as serotonin and catecholamines are involved in the regulation of pituitary hormone secretion, it is obvious that an action of the H3 receptor compounds may be exerted via these H3 heteroreceptors. Only few studies have evaluated this heteroreceptor action. It has been excluded that the effect of the H3 receptor agonists is due to an effect on H3 receptors located on serotonergic neurons, while an effect on catecholaminergic neurons has yet not been excluded. 

Ronken E, Mulder AH, Schoffelmeer ANM (1993) Chronic activation of mu and kappa-opioid receptors in cultured catecholaminergic neurons from rat brain causes neuronal supersensitivity without receptor desensitization. J Pharmacol Exp Ther 268 595-9 Schlicker E, Kathmann M (2001) Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 22 565-572... 

Palmer AM, Francis PT, Bowen DM, Benton JS, Neary D, Mann DM, Snowden JS (1987) Catecholaminergic neurones assessed ante-mortem in Alzheimer s disease. Brain Res. 414 365-375. 

Bonnin, A., de Miguel, R., Rodriguez-Manzaneque, J. C., Femandez-Ruiz, J. J., Santos, A., and Ramos, J. A. (1994). Changes in tyrosine hydroxylase gene expression in mesencephalic catecholaminergic neurons of immature and adult male rats perinatally exposed to cannabinoids. Brain Res. Dev. Brain Res. 81, 147-150. 

Kosaka T, Kosaka K, Hataguchi Y, Nagatsu I, Wu JY, Ottersen OP, Storm-Mathisen J, Hama K (1987) Catecholaminergic neurons containing GABA-like and/or glutamic acid decarboxylase-like immunoreactivities in various brain regions of the rat. Exp Brain res 55 191-210. 

Myers RD, Melchior CL (1975) Alcohol drinking in the rat after destruction of serotoninergic and catecholaminergic neurons in the brain. Res Comm Chem Pathol Pharmacol 70 363-378. 

Selemon LD, Sladek JR (1986) Diencephalic catecholaminergic neurons (A-ll, A-12, A-13, A-14) show divergent changes in the aged rat. J Comp Neurol 254 113-124. 

Pearson J, Halliday G, Sakamoto N, Michel J-P (1990) Catecholaminergic neurons. In Paxinos G (Ed), The Human Nervous System, pp. 1023-1049. Academic Press, Inc., San Diego, New York. 

Dopamine /3-hydroxylase is a monoxygenase that catalyzes the hydroxylation of dopamine to form norepinephrine. This enzyme is localized in the chromaffin granules of the adrenal medulla and in the storage vesicles of central and peripheral catecholaminergic neurons. Since these compounds are unstable, this activity is often assayed by following the formation of octopamine from tyramine. For example, in the assay developed by Feilchenfeld et al. (1982), the reactant tyramine was separated from the product octopamine by reversed-phase, ion-paired HPLC (/uBondapak C18 using a mobile phase of 17% (v/v)... 

The substantially higher potency of (-)-BPAP than (-)-deprenyl in enhancing the activity of catecholaminergic neurons... 

To test a compound s ability to enhance the acquisition of CARs in the shuttle box, it is necessary to select proper training conditions. In the case in which the rat was trained with 100 trials per day, the acquisition of CARs reached an 80% level and the EFs approached or reached the zero level. To demonstrate the highly significant enhancer effect of (-)-BPAP on the mesencephalic catecholaminergic neurons in vivo, we trained the rat with 100 trials per day, blocked the acquisition of CARs by pretreating the rats with tetrabenazine, and restored the learning ability with the simultaneous administration of (-)-BPAP. Table 3.1 shows that (-)-BPAP antagonized the effect of tetrabenazine in the rats. 

Table 3.1. Because of its enhancer effect on catecholaminergic neurons, (-)-BPAP antagonized tetrabenazine-induced learning deficit in rats trained in the shuttle box...

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