Influences of Catecholamine Contents on Tetrahydrobiopterin Metabolism

Pteridines ◽  
1998 ◽  
Vol 9 (1) ◽  
pp. 39-43
Author(s):  
Hiroshi Kuzuya ◽  
Hideo Sakamoto ◽  
Ko Fujita
Keyword(s):  
Nerve Growth Factor ◽  
The Other ◽  
Acid Decarboxylase ◽  
Catecholamine Metabolism ◽  
Decarboxylase Inhibitor ◽  
Amino Acid Decarboxylase ◽  
Comt Inhibitor ◽  
Dopamine Content ◽  
Pheochromocytoma Pc12 ◽  
Inhibitor Treatment

Summary The influence of changes in catecholamine metabolism on tetrahydrobiopterin biosynthesis was investigated in cultured rat pheochromocytoma PC12 cells. The increase in the cellular dopamine content after treatment with the MAO-COMT inhibitor or dopamine produced decreases in the GTP-cy-clohydrolase I (GTPCH-I) activity and total biopterin content. On the contrary, the catecholamine increase after treatment with nerve growth factor produced increases in the GTPCH -I activity and total biopterin content. On the other hand, the decrease in the dopamine content after tyrosine hydroxylase (TH) inhibitor treatment produced decreases in the GTPCH-I activity and total biopterin content, but the catecholamine decrease (the DOPA content increased about 3.4-fold) after aromatic L-amino acid decarboxylase inhibitor treatment produced a decrease in the GTPCH-I activity. These results suggest that an increase in dopamine content that is not directly related to the action of TH plays a role in down-regulation of tetrahydrobiopterin biosynthesis and that when the changes in catecholamine metabolism are strongly associated with the action of TH, tetrahydrobiopterin biosynthesis is regulated depending on the necessity for TH.

Changes in serotonin contents in brain affect metabolic heat production of rabbits in cold

1978 ◽  
Vol 235 (1) ◽  
pp. R41-R47
Author(s):  
M. T. Lin ◽  
I. H. Pang ◽  
S. I. Chern ◽  
W. Y. Chia
Keyword(s):  
Blood Flow ◽  
Amino Acid ◽  
Heat Loss ◽  
Acid Decarboxylase ◽  
Evaporative Heat Loss ◽  
Decarboxylase Inhibitor ◽  
Ambient Temperatures ◽  
Amino Acid Decarboxylase ◽  
Metabolic Heat ◽  
Normal Limits

Elevating serotonin (5-HT) contents in brain with 5-hydroxytryptophan (5-HTP) reduced rectal temperature (Tre) in rabbits after peripheral decarboxylase inhibition with the aromatic-L-amino-acid decarboxylase inhibitor R04-4602 at two ambient temperatures (Ta), 2 and 22 degrees C. The hypothermia was brought about by both an increase in respiratory evaporative heat loss (Eres) and a decrease in metabolic rate (MR) in the cold. At a Ta of 22 degrees C, the hypothermia was achieved solely due to an increase in heat loss. Depleting brain contents of 5-HT with intraventricular, 5,7-dihydroxytryptamine (5,7-DHT) produced an increased Eres and ear blood flow even at Ta of 2 degrees C. Also, MR increased at all but the Ta of 32 degrees C. However, depleting the central and peripheral contents of 5-HT with p-chlorophenylalanine (pCPA) produced lower MR accompanied by lower Eres in the cold compared to the untreated control. Both groups of pCPA-treated and 5,7-DHT-treated animals maintained their Tre within normal limits. The data suggest that changes in 5-HT content in brain affects the MR of rabbits in the cold. Elevating brain content of 5-HT tends to depress the MR response to cold, while depleting brain content of 5-HT tends to enhance the MR response to cold.

Induction of neurite formation in PC12 cells by microinjection of proto-oncogenic Ha-ras protein preincubated with guanosine-5'-O-(3-thiotriphosphate)

1987 ◽  
Vol 7 (12) ◽  
pp. 4553-4556
Author(s):  
T Satoh ◽  
S Nakamura ◽  
Y Kaziro
Keyword(s):  
Nerve Growth Factor ◽  
Pc12 Cells ◽  
Morphological Differentiation ◽  
The Other ◽  
P21 Protein ◽  
Ras Protein ◽  
Oncogenic Ras ◽  
Neurite Formation ◽  
Pheochromocytoma Pc12 ◽  
Oncogenic Protein

Rat pheochromocytoma (PC12) cells differentiate to neuronal cells in response to nerve growth factor. It has been shown that microinjection of oncogenic but not proto-oncogenic p21 protein induces morphological differentiation in PC12 cells (D. Bar-Sagi and J. R. Feramisco, Cell 42:841-848, 1985). In this paper we describe a recombinant human proto-oncogenic Ha-ras protein which can effectively induce neurite extension of PC12 cells when microinjected as a complex with guanosine-5'-O-(3-thiotriphosphate). The protein was found to be less effective when complexed with GTP. On the other hand, an oncogenic ras protein coinjected with guanosine-5'-O-(2-thiodiphosphate) was entirely inactive. These results indicate that the binary p21-GTP complex, but not the p21-GDP complex, is effective in inducing differentiation in PC12 cells, irrespective of the oncogenic or the proto-oncogenic protein.

scholarly journals Induction of neurite formation in PC12 cells by microinjection of proto-oncogenic Ha-ras protein preincubated with guanosine-5'-O-(3-thiotriphosphate).

1987 ◽  
Vol 7 (12) ◽  
pp. 4553-4556 ◽  
Author(s):  
T Satoh ◽  
S Nakamura ◽  
Y Kaziro
Keyword(s):  
Nerve Growth Factor ◽  
Pc12 Cells ◽  
Morphological Differentiation ◽  
The Other ◽  
P21 Protein ◽  
Ras Protein ◽  
Oncogenic Ras ◽  
Neurite Formation ◽  
Pheochromocytoma Pc12 ◽  
Oncogenic Protein

Rat pheochromocytoma (PC12) cells differentiate to neuronal cells in response to nerve growth factor. It has been shown that microinjection of oncogenic but not proto-oncogenic p21 protein induces morphological differentiation in PC12 cells (D. Bar-Sagi and J. R. Feramisco, Cell 42:841-848, 1985). In this paper we describe a recombinant human proto-oncogenic Ha-ras protein which can effectively induce neurite extension of PC12 cells when microinjected as a complex with guanosine-5'-O-(3-thiotriphosphate). The protein was found to be less effective when complexed with GTP. On the other hand, an oncogenic ras protein coinjected with guanosine-5'-O-(2-thiodiphosphate) was entirely inactive. These results indicate that the binary p21-GTP complex, but not the p21-GDP complex, is effective in inducing differentiation in PC12 cells, irrespective of the oncogenic or the proto-oncogenic protein.

The “Sick-but-not-Dead” Phenomenon Applied to Catecholamine Deficiency in Neurodegenerative Diseases

2020 ◽  
Vol 40 (05) ◽  
pp. 502-514
Author(s):  
David S. Goldstein
Keyword(s):  
Lewy Body ◽  
Lewy Bodies ◽  
Dopamine Metabolism ◽  
Major Constituent ◽  
Acid Decarboxylase ◽  
Amino Acid Decarboxylase ◽  
Catecholaminergic Neurons ◽  
Disease States ◽  
Dopamine Content ◽  
Lewy Body Diseases

AbstractThe catecholamines dopamine and norepinephrine are key central neurotransmitters that participate in many neurobehavioral processes and disease states. Norepinephrine is also the main neurotransmitter mediating regulation of the circulation by the sympathetic nervous system. Several neurodegenerative disorders feature catecholamine deficiency. The most common is Parkinson's disease (PD), in which putamen dopamine content is drastically reduced. PD also entails severely decreased myocardial norepinephrine content, a feature that characterizes two other Lewy body diseases—pure autonomic failure and dementia with Lewy bodies. It is widely presumed that tissue catecholamine depletion in these conditions results directly from loss of catecholaminergic neurons; however, as highlighted in this review, there are also important functional abnormalities in extant residual catecholaminergic neurons. We refer to this as the “sick-but-not-dead” phenomenon. The malfunctions include diminished dopamine biosynthesis via tyrosine hydroxylase (TH) and L-aromatic-amino-acid decarboxylase (LAAAD), inefficient vesicular sequestration of cytoplasmic catecholamines, and attenuated neuronal reuptake via cell membrane catecholamine transporters. A unifying explanation for catecholaminergic neurodegeneration is autotoxicity exerted by 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediate in cytoplasmic dopamine metabolism. In PD, putamen DOPAL is built up with respect to dopamine, associated with a vesicular storage defect and decreased aldehyde dehydrogenase activity. Probably via spontaneous oxidation, DOPAL potently oligomerizes and forms quinone-protein adducts with (“quinonizes”) α-synuclein (AS), a major constituent in Lewy bodies, and DOPAL-induced AS oligomers impede vesicular storage. DOPAL also quinonizes numerous intracellular proteins and inhibits enzymatic activities of TH and LAAAD. Treatments targeting DOPAL formation and oxidation therefore might rescue sick-but-not-dead catecholaminergic neurons in Lewy body diseases.

A decreased tubular uptake of dopa results in defective renal dopamine production in aged rats

1995 ◽  
Vol 268 (6) ◽  
pp. F1087-F1092 ◽  
Author(s):  
I. Armando ◽  
S. Nowicki ◽  
J. Aguirre ◽  
M. Barontini
Keyword(s):  
Renal Cortex ◽  
Membrane Vesicles ◽  
Acid Decarboxylase ◽  
Amino Acid Decarboxylase ◽  
Dopamine Content ◽  
Male Wistar Rats ◽  
Urinary Dopamine ◽  
Old Rats ◽  
Effects Of Aging ◽  
Renal Dopamine

A major proportion of urinary dopamine derives from the renal decarboxylation of circulating dopa. This study evaluates the effects of aging on renal production of dopamine using 3- and 12-mo-old male Wistar rats. Urinary excretion of Na+, norepinephrine (NE), 3,4-dihydroxyphenylglycol, and dopa were similar in the two groups. Urinary dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were lower in older animals (dopamine, 20 +/- 6 vs. 47 +/- 7 nmol/24 h, P < 0.001; DOPAC, 142 +/- 36 vs. 304 +/- 56 nmol/24 h, P < 0.03). Urinary 3-O-methyldopa (OM-dopa) was higher in 12-mo-old rats (6.2 +/- 2.0 vs. 3.3 +/- 0.20 nmol/24 h, P < 0.03). Levels of dopa and NE in renal cortex from 12-mo-old rats were higher (P < 0.001) than in younger animals. Dopamine content in renal cortex from 3-mo-old rats was 295 +/- 64 pmol/g, whereas it was undetectable in 12-mo-old animals. Aromatic-L-amino-acid decarboxylase and monoamine oxidase activities were higher (P < 0.001) in renal cortex from 12-mo-old animals. Catechol-O-methyltransferase activity was similar in both groups. The uptake of dopa by the luminal membrane was explored using brush-border membrane vesicles. The Na(+)-gradient-driven (100 mM) uptake of dopa into vesicles from 3-mo-old animals showed at 10 s an overshoot threefold greater than the equilibrium uptake. The overshoot was blunted in 12-mo-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

An aromatic l-amino acid decarboxylase inhibitor blocks l-dopa-induced air-stepping in neonatal rats

1996 ◽  
Vol 94 (2) ◽  
pp. 234-237
Author(s):  
Carlos O. Arnaiz ◽  
Lynette L. Taylor ◽  
Donald J. Stehouwer ◽  
Carol Van Hartesveldt
Keyword(s):  
Amino Acid ◽  
Acid Decarboxylase ◽  
Neonatal Rats ◽  
Decarboxylase Inhibitor ◽  
Amino Acid Decarboxylase
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