Sources and Significance of Plasma Levels of Catechols and Their Metabolites in Humans

Abstract

Human plasma contains several catechols, including the catecholamines norepinephrine, epinephrine, and dopamine, their precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), and their deaminated metabolites, dihydroxyphenylglycol, the main neuronal metabolite of norepinephrine, and dihydroxyphenylacetic acid, a deaminated metabolite of dopamine. Products of metabolism of catechols include 3-methoxytyrosine (from L-DOPA), homovanillic acid and dopamine sulfate (from dopamine), normetanephrine, vanillylmandelic acid, and methoxyhydroxyphenylglycol (from norepinephrine), and metanephrine (from epinephrine). Plasma levels of catechols and their metabolites have related but distinct sources and therefore reflect different functions of catecholamine systems. This article provides an update about plasma levels of catechols and their metabolites and the relevance of those levels to some issues in human health and disease.Near the end of the 19th century, soon after the description of the profound cardiovascular effects of injected adrenal extract and the purification and identification of epinephrine as the vasoactive principal of the adrenal gland, researchers began to develop chemical means to assess activity of what came to be called the sympathoadrenomedullary system. The first chemical method for such measurement was colorimetric, based on the unusual susceptibility of epinephrine to oxidize, forming a brownish compound called "adrenochrome". Early attempts to measure circulating levels of epinephrine and related compounds chemically failed, mainly because the potency of epinephrine corresponds to very low normal concentrations in the bloodstream. Bioassays such as used by the great American physiologist, Walter B. Cannon were the first to detect successfully epinephrine release into the circulation. Cannon later developed and exploited a preparation based on the magnitude of the increase in heart rate in animals with denervated hearts; abolition of the increase by adrenalectomy confirmed the hormone's adrenal source. Subsequent chemical methods depended on fluorescence detection (after the trihydroxyindole reaction or ethylenediamine condensation) or radioenzymatic assays (after methylation with S-adenosylmethionine and catechol-Omethyltransferase). Ironically, current sensitive chemical methods using liquid chromatography with electrochemical detection depend on the same catechol oxidation as did the original colorimetric method.For almost the whole of the first half of the last century, epinephrine was the only catecholamine to receive attention. Cannon proposed-erroneously-that epinephrine was not only the main vasoactive hormone released by the adrenal gland but also the chemical messenger released from sympathetic nerves. This fit with his concept of a unitary sympathoadrenomedullary system, which would help maintain homeostasis (a word he coined) during emergencies but would not be necessary in day-to-day life. Fifty years after the discovery of epinephrine, norepinephrine, rather than epinephrine, was fi...

β2‐Adrenergic receptor regulation of human neutrophil function is sexually dimorphic

“…While plasma levels of endogenous catecholamines, such as adrenaline and noradrenaline, are relevant to b 2 -adrenergic receptor activity, we found no gender difference in the levels of catecholamines, in agreement with the literature (Davis et al, 2000;Geelen et al, 2002). Plasma catecholamine concentrations usually range around 1 Â 10 À9 M for noradrenaline and 0.2 Â 10 À9 M for adrenaline, but increase in response to stress and anxiety (Swain, 2000), or hypoglycemia (Goldstein et al, 2003). In our study, blood samples were obtained from subjects in a normal laboratory setting (and not from supine subjects in a light-and noise-controlled room), and we observed plasma catecholamine concentrations higher than some other reports, consistent with mild stress associated with the venipuncture procedure (Pacak et al, 1998).…”

“…In our study, blood samples were obtained from subjects in a normal laboratory setting (and not from supine subjects in a light-and noise-controlled room), and we observed plasma catecholamine concentrations higher than some other reports, consistent with mild stress associated with the venipuncture procedure (Pacak et al, 1998). However, it should also be noted that there is a large variation of published catecholamine plasma concentration obtained from healthy humans (Goldstein et al, 2003).…”

“…Recently, it has been recognized that resolution of the inflammatory response depends on several active processes, with the role of glucocorticoids being the most extensively studied (Goulding et al, 1998). Our novel findings suggest an additional inflammatory control system, dependent on release of catecholamines from the sympathoadrenal axis.…”

Synthetic calibrators for the analysis of total metanephrines in urine: Revisiting the conditions of hydrolysis

“…Catecholamines (norepinephrine, epinephrine and dopamine) are important hormones and neurotransmitters involved in cardiovascular and metabolic homeostasis [1]. The physiological effects of catecholamines are terminated by several conjugation pathways including 3-O-methylation followed by sulfonation at the 4-hydroxy group [1].…”

“…The physiological effects of catecholamines are terminated by several conjugation pathways including 3-O-methylation followed by sulfonation at the 4-hydroxy group [1]. Norepinephrine and epinephrine are 3-O-methylated by catechol-O-methyltransferase (COMT) into normetanephrine (NMN) (Supplementary data, 2) and metanephrine (MN) (Supplementary data, 1), respectively [1]. Likewise, methoxytyramine (MT) (Supplementary data, 3) is the O-methylated form of dopamine.…”