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Effects of Catecholamine Metabolites on Beta-Adrenoceptor-Mediated Relaxation of Smooth Muscle: Evaluation in Mouse and Guinea-Pig Trachea and Rat Aorta.
Biol Pharm Bull
September 2020
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
Article Synopsis
- The study investigated how catecholamine metabolites affect smooth muscle relaxation in tracheas and aorta of different animals, revealing that metadrenaline notably relaxed guinea pig trachea.
- In the presence of enzyme inhibitors, normetadrenaline and metadrenaline showed mixed effects on isoprenaline-induced relaxation, highlighting their complex interactions.
- The findings suggest that these metabolites can either enhance or inhibit β-adrenoceptor-mediated relaxation, potentially contributing to conditions like pheochromocytoma associated with high catecholamine levels.
Determination of catecholamines and related compounds in mouse urine using column-switching HPLC.
Analyst
April 2016
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
We have developed an analytical method for the determination of catecholamines and related compounds in mouse urine by column-switching HPLC. Selective extraction of the catechol compounds was performed using a precolumn modified with phenylboronic acid, which has a pH dependent affinity for the catechol structures. The pretreatment buffer, which facilitated binding of the catechols to the precolumn, was optimized to ensure high analyte recoveries and good peak shapes.
View Article and Find Full Text PDFNorepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus.
J Neurochem
November 2015
Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi, Japan.
In order to elucidate the chemical structure of black to brown pigments, neuromelanins (NMs), in the substantia nigra (SN) and the locus coeruleus (LC) in the central nervous system of humans and other mammalian species during aging, chemical degradative methods are powerful tools. HPLC analysis after hydroiodic acid hydrolysis detected aminohydroxyphenylethylamines, aminohydroxyphenylacetic acids, and aminohydroxyethylbenzenes, which confirmed that SN-NM and LC-NM contain melanin derived not only from dopamine and norepinephrine (NE) but also from several other catecholic metabolites, such as 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxymandelic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylethylene glycol, in addition to the corresponding Cys-derivatives in varying degrees. However, hydroiodic acid hydrolysis showed that LC-NM produced the same degradation products as were detected in SN-NM.
View Article and Find Full Text PDFDevelopment of analytical method for catechol compounds in mouse urine using hydrophilic interaction liquid chromatography with fluorescence detection.
J Chromatogr B Analyt Technol Biomed Life Sci
March 2015
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. Electronic address:
An analytical method for catecholamines and related compounds using hydrophilic interaction liquid chromatography (HILIC) with native fluorescence detection has been developed. We found that ZIC-cHILIC with phosphorylcholine was suitable for the separation of catechol compounds with good peak shapes among six different HILIC columns (Inertsil SIL, Inertsil Amide, Inertsil Diol, TSKgel NH2-100, ZIC-HILIC, and ZIC-cHILIC). Using ZIC-cHILIC, eight catechol compounds (dopamine, epinephrine, norepinephrine, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylglycol, 3,4-dihydroxymandelic acid, and internal standard 3,4-dihydroxybenzylamine) were separated within 15min.
View Article and Find Full Text PDFEffects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS.
J Clin Pharmacol
January 2011
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA.
Background: L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect.
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