References

Quest for the basic plan of nervous system circuitry. Brain Research Reviews. 2007 55 356-72. 2 Schwann T. Mikroskopische Untersuchungen ber die bereinstimmung in der Struktur und dem Wachstum der Thiere und Pflanzen. Berlin. Sander'schen Buchhandlung, 1839. 3 Vulpian EF. Lecons sur la Physiologie Generale et Comparee du Systeme Nerveux. Bailliere, Paris, 1866. 4 DuBois-Reymond, E. (1875-1877), Gesammette Abhandtungen fur allegememen Muskel--undNervenphysik Veil v. Comp.,...

Vitamin C Synthesis and Transport

Vitamin C is an essential nutrient required for all eukarotic organisms and is especially concentrated in the mammalian nervous system 98,99 . Vitamin C enters mammalian cells, including neurons, by two possible mechanisms. First, ascorbic acid (AA, oxidized Vitamin C) can be transported by a sodium-dependent Vitamin C transporter (SVCT), of which there are two known isoforms, SVCT1 and SVCT2 100-102 . These mammalian symporters are membrane-associated glycoproteins with 12 transmembrane...

HPLC with Electrochemical Detection Hplcecd

The HPLC-ECD is based on the measurement of current resulting from the flow of electrons produced by the oxidation or reduction of electrochemically active substances on the surface of an electrode 60 . Catecholamines can be oxidized to corresponding quinones by the loss of two electrons in the detector electrode, therefore, they provide the basis for their detection by electrochemical detection. However, other compounds that do not undergo oxidation unless large electric potentials are applied...

Competitive and Noncompetitive Antagonists

Antagonists interact with receptors, but unlike agonists, have no intrinsic activity. Thus, the drug-receptor complex does not produce a biological response. However, since antagonists occupy the receptor, they will inhibit the interaction between the agonist and the receptor according to the principles of mass action, resulting in an inhibition of the agonist-induced pharmacological response. Endogenous compounds such as hormones, neurotransmitters and autacoids are agonists and elicit a...

Turnover Studies of Dopamine and Dopac

An early suggestion of the hypothesis of two storage compartments for dopamine came from studies on the rate of disappearance of dopamine from the striatum after inhibition of dopamine synthesis by a-methyl-p-tyrosine. The kinetics of disappearance reported by Javoy and Glowinski 21 showed an initial rapid decrease in tissue dopamine, followed by an increase in tissue dopamine, followed by a gradual decline of dopamine over a long period of time. These data were interpreted as indicative of two...

Volume Transmission

Descarries reported naked CNS axon terminals (lacking adjacent post-synaptic elements) labeled by 3H- noradrenaline and in later studies with 3H- 5-hydroxytryptamine 147 . Only 5 of the varicosities formed with 5-HT were associated with identifiable synapses 148 . The suggestion of transmitter release from non-synaptic sites led Agnati and Fuxe to construct a theory of volume transmission 149,150 . Jansson and colleagues at Karolinska Institute studied both transmitter releasing 5-HT axon...

What Has 6Hydroxydopamine Taught Us About Parkinsons Disease

University of Pittsburgh, Pittsburgh, PA 15260, USA. 6-Hydroxydopamine was first identified in 1959. By the early 1970s, this selective toxin for norepinephrine and dopamine neurons had become the principal tool by which laboratory studies of Parkinson's disease were performed, due largely to the pioneering work of Urban Ungerstedt and Norman Uretsky. The toxin has taught us an great deal about the possible causes, pathophysiology, and treatments of the disease. Although improved models are...

Trace Amine Associated Receptors

In 2001 two groups independently identified a family of novel G-protein coupled receptors some of which appeared to selectively respond to trace amines 3,4 , thus providing a viable target for previously observed responses. As other members of this new receptor family were subsequently identified, a number of potential nomenclatures appeared in the literature. Recently, three proposals for a systematic naming system for this family of receptors have been provided 6,9,10 . The International...

Neurotransmitter Receptor Regulation of aaad

Cumulative evidence suggests that acute or chronic blockade of D1- and D2-like receptors increase the activity of AAAD in rodent striatum (Table 4). Selective or mixed D1, D2, D3 or D4 antagonists administered acutely, all elevate striatal AAAD activity, and a similar effect has been observed with multireceptor drugs displaying affinity for D2-like receptors, such as spiperone and clozapine 54,56,60,66,79 . In general, there is an early transient activation and a late induction, and the latter...

Legacy from the Past

Ancient plant products used by various civilizations and cultures provided a rich source of medicines and lead drugs 1-4 . The collaboration in the early 1800s between the pharmacist-chemist Pelletier and the physiologist Magendie, on the pharmacological evaluation of various alkaloids such as strychnine, emetine, and quinine may have set the stage for the science of medicinal chemistry 5 . Magendie understood the concept that certain substances could produce specific changes in organ function....

False Transmitters

Sourkes reported that a-methylDOPA inhibited DOPA decarboxylase in 1954. Its antihypertensive actions were initially ascribed to this effect. However, decarboxylase inhibition did not explain its antihypertensive action. Drug administration led to a-methyldopamine storage in the brain and sympathetic nerves. Carlsson and Lindqvist contrasted reserpine-induced monoamine depletion with that caused by the DOPA analogs, a-methyldopa and a-methyl-m-tyrosine 39 . Carlsson and others proposed that...

The Crises of the Newborn Norepinephrine is Still a Necessity

Rescued TH-null mutants and the few that survive birth without supplementation are born with normal weight, length, appearance, and blood glucose levels. However they've no sooner survived the hypoxic crises of their life in utero, but they encounter a new crisis life ex utero. The untreated TH-null pups, at first indistinguishable from their littermates, live days to weeks but not beyond weaning unless they are specially treated. Life of the newborn is similar to that of the fetus in that...

Receptor Pharmacology

Our knowledge regarding the pharmacological characteristics of octopamine receptors is copious, whereas we know only very basic aspects about tyramine receptor pharmacology. Thus tyramine receptors are in a situation that is very similar for most invertebrate bioamine receptors we have no, or only very few information regarding their pharmacological characteristics. One major drawback is the lack of highly potent and specific agonists for tyramine receptors in general. The major classification...

Dopac Da and DA Turnover

Mean values and associated statistics for DOPAC and DA tissue concentrations (pg mg protein) are presented in Table 2. Two-way ANOVA indicated no significant effects of Treatment Group, Drug, or their interaction on analyte content in the prefrontal cortex. However, a significant Treatment Group X Drug interaction was found for nucleus accumbens DA content. This effect was due to significantly decreased DA content in the E2 group treated with apomorphine when compared to both the E2 group...

Biogenic Amines in Neurodegenerative and Neuropsychiatric Diseases

Neurodegenerative and neuropsychiatric diseases are a group of neurological disorders with heterogeneous clinical and pathological expressions affecting specific subsets of neurons in specific functional anatomic regions of brain and spinal cord. Thus, in AD neurodegeneration mainly occurs in the nucleus basalis and hippocampal area, whereas in PD dopaminergic neurons in the substantia nigra undergo neurodegeneration. In HD neurodegeneration occurs in striatal medium spiny neurons and motor...

High Performance Liquid Chromatography with Fluorometric Detection

The fluorometric detection is based on the phenomenon in which light from the ultraviolet spectrum is absorbed by a substance, and the fluorescence is emitted in the visible spectrum. Biogenic amines can absorb light energy that can be dissipated by the fluorescence emission. The number of photons in light emission is proportional to the number of molecules involved, referring to the concentration of fluorescent substances in the sample. The HPLC separation combined with the enhanced...

Determination of Octopamine by Gas Chromatography Coupled with Mass Spectrometry GCMS

Gas chromatography (GC) and mass spectrometry (MS) make an effective combination tool for detecting levels of bioamines. GC-MS relies not only on chromatographic retention but also on molecular mass to ascertain identity 85 . Therefore it offers a significant advantage over methods such as HPLC-ECD, which rely on retention time alone. In GC procedure, a small amount of the sample to be analyzed is drawn up into a syringe. The injector is set to a temperature higher than the components' boiling...

Hydroxydopamine Meets pd

The first animal models of PD involved drugs such as reserpine that depleted the brain of biogenic amines and surgical lesions that caused the destruction of the medial forebrain bundle through which the nigrostriatal projection runs. With the realization that the motor symptoms caused by these manipulations were due to the loss of DA came the wish to produce such a loss in a more specific manner. The tool that would allow the field to accomplish this came quite by accident with the discovery...

Mitochondrial Electron Transport Chain and Oxidative Stress in pd

Mitochondria are primary organelles responsible for ATP generation for cellular activities. The mitochondrial generation of energy is regulated by five electron transport chain complexes located in the inner mitochondrial membrane. The redox energy from reduced electron carriers, nicotinamide adenine dinucleotide NADH and flavin adenine dinucleotide FADH2 , is transferred to O2 terminal electron acceptor in the chain to produce H2O via four respiratory chain complexes. The establishment of a...

Modulation of Neurotransmission by Docosahexaenoic Acid

DHA modulates and facilitates neurotransmission through its effect on a variety of receptors including dopaminergic, noradrenergic, P-adrenergic glutamatergic, and serotonergic neurotransmitter receptors. In addition, DHA also modulates insulin, retinoid and TGF-P receptors in nuclear and non-nuclear compartments Table 1 22-25 . DHA modulates dopaminergic and serotonergic neurotransmission in rat frontal cortex, and a chronic depletion of DHA changes dopamine metabolism by altering dopamine...

Quantification of Octopamine by Radioenzymic Assay

The original radioenzymic assay used for the determination of octopamine is based on the -methylation of the 9-hydoxylated amines such as octopamine and phenylethanolamine to their N-methyl derivatives by the enzyme phenylethanolamine-N-methyltransferase PNMT , using radioactively labeled S-adenosylmethionine as a methyl donor in the reaction mixture Figure 2 46 . In this assay, labeled methyl derivative of octopamine N-methyloctopamine, synephrine is extracted in a mixture of toluene-isoamyl...

Tyramine Betahydroxylase

The Drosophila melanogaster Tbh gene DmTbh encodes a 660 amino acid polypeptide with a predicted mass of 76,000 Da. The protein encoded by DmTbh is 35-54 identical and 54-70 similar to other invertebrate Tbh proteins now predicted or described including Drosophila sp. A. mellifera, Anopheles gamiae, Tribolium castaneum, Nasonia vitripennis and Caenorhabditis elegans , and is ca. 41 identical and 57 similar to the vertebrate enzyme Dbh Figure 2 50 . Tbh, Dbh, and PHM belong to a group of copper...