Roles of catechol neurochemistry in autonomic function testing

Abstract

Catechols are a class of compounds that contain adjacent hydroxyl groups on a benzene ring. Endogenous catechols in human plasma include the catecholamines norepinephrine, epinephrine (adrenaline), and dopamine; the catecholamine precursor DOPA, 3,4-dihydroxyphenylglycol (DHPG), which is the main neuronal metabolite of norepinephrine; and 3,4-dihydroxyphenylacetic acid (DOPAC), which is the main neuronal metabolite of dopamine. In the diagnostic evaluation of patients with known or suspected dysautonomias, measurement of plasma catechols is rarely diagnostic but often is informative. This review summarizes the roles of clinical catechol neurochemistry in autonomic function testing.

Keywords: Autonomic; Catechol; DHPG; Norepinephrine; Sympathetic.

Figure 1:. Catechols look like cats.

The benzene ring of catechols with its two adjacent hydroxyl groups resembles the head of a cat.

Figure 2:. Chemical structures of catechols found in human plasma.

Additional abbreviations: Cys = 5-S-cysteinyl; DOPAC = 3,4-dihydroxyphenylacetic acid; DHPG = 3,4-dihydroxyphenylglycol

Figure 3:. Sympathoneural sources of plasma levels of catechols.

Abbreviations: ALDH = aldehyde dehydrogenase; AR = aldehyde/aldose reductase; Cys-DA = 5-S-cysteinyldopamine; Cys-DOPA = 5-S-cysteinylDOPA; DA = dopamine; DBH = dopamine-beta-hydroxylase; DHPG = dihydroxyphenylglycol; DOPAC = dihydroxyphenylacetic acid; DOPAL = dihydroxyphenylacetaldehyde; DOPEGAL = dihydroxyphenylglycolaldehyde; LAAAD = L-aromatic-amino-acid decarboxylase; MAO = monoamine oxidase; NE = norepinephrine; NET = cell membrane norepinephrine transporter; TH = tyrosine hydroxylase; VMAT = vesicular monoamine transporter.

Figure 4:. Irwin J. (“Irv”) Kopin and Julius (“Julie”) Axelrod.

The photo on the left was taken after Axelrod’s Nobel Prize was announced in 1970 (the third person is Dr. Fred Goodwin). The photo on the right shows Julie and Irv many years later in 2003.

Figure 5:. Vesicular localization of DBH in a human sympathetic ganglionic neuron.

In this immunofluorescence micrograph green corresponds to DBH, red to TH, and yellow to co-localized DBH and TH. Punctate regions of green show vesicular localization of DBH without TH (Image courtesy of R. Isonaka).

Figure 6:. Takotsubo cardiopathy.

During diastole (a) the heart appears normal, but during systole (b) the absence of apical left ventricular contraction and presence of basal contraction give the heart the appearance of a takotsubo (c).

Figure 7:. The “cheese effect.”

In the setting of blockade of MAO-A or both MAO-A and MAO-B, ingested tyramine can reach the liver, the systemic circulation, and sympathetic noradrenergic nerves. Displacement of vesicular NE can then evoke NE release, resulting in paroxysmally increased blood pressure and plasma NE.