Catecholamine Research in the 21ST Century (original) (raw)
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Catecholamine biosynthesis and physiological regulation in neuroendocrine cells
Acta Physiologica Scandinavica, 2000
The catecholamines are widely distributed in mammals and their levels and physiological functions are regulated at many sites. These include their release from neuroendocrine cells, the type and sensitivity of the multiple receptors in target cells, the efficacy of the reuptake system in the secretory cells, and the rates of catecholamine biosynthesis and degradation. In the present review the main focus will be on the more recent studies on the biosynthesis in neuroendocrine cells which involves a specific set of enzymes, with special reference to physiologically important regulatory mechanisms. Eight enzymes of the biosynthetic pathway have now been identified, cloned, expressed as recombinant proteins, characterized with respect to catalytic and regulatory properties, and some of them also crystallized. The identification of the tyrosine hydroxylase catalysed reaction as the rate-limiting step in the normal catecholamine biosynthesis has attracted most attention, both in terms of transcriptional and post-translational regulation. In certain human genetic disorders of catecholamine biosynthesis other enzymes in the pathway may become rate-limiting, notably those involved in the biosynthesis/regeneration of the natural co-factor tetrahydrobiopterin in the tyrosine hydroxylase reaction. The enzymes involved seem to be regulated by a variety of physiological factors, both on a long-term scale and a short-term basis, and include the relative rates of synthesis, degradation and state of activation of the biosynthetic enzymes, notably of tyrosine hydroxylase. Multiple surface receptors and signalling pathways are activated in response to extracellular stimuli and play an essential role in the regulation of catecholamine biosynthesis.
Catecholamines: Knowledge and understanding in the 1960s, now, and in the future
Brain and Neuroscience Advances, 2019
The late 1960s was a heyday for catecholamine research. Technological developments made it feasible to study the regulation of sympathetic neuronal transmission and to map the distribution of noradrenaline and dopamine in the brain. At last, it was possible to explain the mechanism of action of some important drugs that had been used in the clinic for more than a decade (e.g. the first generation of antidepressants) and to contemplate the rational development of new treatments (e.g. l-dihydroxyphenylalanine therapy, to compensate for the dopaminergic neuropathy in Parkinson’s disease, and β1-adrenoceptor antagonists as antihypertensives). The fact that drug targeting noradrenergic and/or dopaminergic transmission are still the first-line treatments for many psychiatric disorders (e.g. depression, schizophrenia, and attention deficit hyperactivity disorder) is a testament to the importance of these neurotransmitters and the research that has helped us to understand the regulation of ...
Catecholamine Metabolism: An Update on Key Biosynthetic Enzymes and Vesicular Monoamine Transporters
Annals of the New York Academy of Sciences, 2002
The catecholamines are widely distributed in mammals and their levels and physiological functions are regulated at many sites. These include their release from neuroendocrine cells, the type and sensitivity of the multiple receptors in target cells, the efficacy of the reuptake system in the secretory cells, and the rates of catecholamine biosynthesis and degradation. In the present review the main focus will be on the more recent studies on the biosynthesis in neuroendocrine cells which involves a specific set of enzymes, with special reference to physiologically important regulatory mechanisms. Eight enzymes of the biosynthetic pathway have now been identified, cloned, expressed as recombinant proteins, characterized with respect to catalytic and regulatory properties, and some of them also crystallized. The identification of the tyrosine hydroxylase catalysed reaction as the rate-limiting step in the normal catecholamine biosynthesis has attracted most attention, both in terms of transcriptional and post-translational regulation. In certain human genetic disorders of catecholamine biosynthesis other enzymes in the pathway may become rate-limiting, notably those involved in the biosynthesis/regeneration of the natural co-factor tetrahydrobiopterin in the tyrosine hydroxylase reaction. The enzymes involved seem to be regulated by a variety of physiological factors, both on a long-term scale and a short-term basis, and include the relative rates of synthesis, degradation and state of activation of the biosynthetic enzymes, notably of tyrosine hydroxylase. Multiple surface receptors and signalling pathways are activated in response to extracellular stimuli and play an essential role in the regulation of catecholamine biosynthesis.
Life Sciences, 1973
This presentation describes the localization, characterization and regulation of dopamine-/3-hydroxylase and of other catecholamine synthesizing enzymes. Three enzymes involved in catecholamine biosynthesis, namely dopamine-/3-hydroxylase (D/3H) aromatic L~amino acid decarboxylase (AADC) and phenylethanolamine N-methyl transferase (PNMT) were purified from bovine adrenal glands . D~iH was also purified from human serum, adrenal glands and pheochromocytoma tumor tissues. The purified enzymes were used to induce the production of immunologically pure antienzymes in rabbits . The latter were utilized for immunochemical studies as well as for localization of catecholamine synthesizing enzymes in peripheral tissue and brain by an indirect immunofluorescence method .
Dopamine β-hydroxylase and the regulation of catecholamine biosynthesis
Life Sciences, 1973
This presentation will briefly reviéw some methods for catecholamine investigation in man, focusing in particular on attempts to study catecholaminerelated processes at the human cellular level, with examples from current studies. Unlike animal preparations in which catecholamine metabolism can be
Cloning of two additional catecholamine receptors from rat brain
FEBS Letters, 1990
An approach based on the polymerase chain reaction (PCR) was used to isolate additional members of the G-linked receptor family from a rat striatal lgtI1 cDNA library. Priming with one degenerate probe corresponding to highly conserved consensus sequences in the third transmembrane (TM) domain of 15 G-linked receptors and sequences in the phage vector resulted in one clone (G-13) encoding a dopamine D2 receptor variant with a 29 amino acid insert in the third cytoplasmic loop. In addition, the amino acid sequence encoded by clone G-36 contained conserved sequences characteristic of the G-linked class of receptors and displayed sequence homology in TM domains with the &adrenergic receptor (48%). Two conserved serine residues in TM5 postulated to be part of a ligand binding site in the adrenergic receptor, suggests that G-36 encodes a catecholaminergic receptor. Northern blot analysis contlrmed the expression of G-36 in rat brain, but not in kidney, heart and lung. Several strong hybridizing bands to G-36 were obtained in both human and rat genomic DNA. The general PCR strategy employed here should prove to be extremely useful for the isolation of other members of the G-linked receptor family.
Proceedings of the National Academy of Sciences, 1983
mRNA for dopamine 3-hydroxylase [3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (fl-hydroxylating), EC 1.14.17.1] has been partially purified from poly(A)+ mRNA isolated from a rat pheochromocytoma cell line. Shared antigenic determinants between tyrosine hydroxylase and dopamine f-hydroxylase allowed us to obtain enriched fractions of dopamine 13hydroxylase mRNA by immunoprecipitating translated mRNA products with tyrosine hydroxylase antisera. The enriched dopamine (-hydroxylase mRNA was used to synthesize the corresponding cDNAs, which were then cloned in the Pst I site of pBR322. Recombinant colonies were characterized by an in situ colony immunoassay and hybrid-selected translation. In vitro translation of the mRNA selected from one recombinant clone produced a protein of 75,000 daltons that comigrated with authentic dopamine 3-hydroxylase. Partial proteolysis of both authentic dopamine 3-hydroxylase and the protein encoded by the recombinant clone produced identical peptide patterns.