Nguyen T. Buu

ANF-like peptide(s) in the peripheral autonomic nervous system.

The recent demonstration of the atrial natriuretic factor (ANF) within the brain has been extended in the present study by the additional localization of ANF-like activity in the peripheral nervous structures. Using a sensitive radioimmunoassay, it was possible to detect ANF-like immunoreactive peptide(s) in crude and chromatographically separated extracts of parasympathetic rat ganglia. The partially purified ANF-like peptide exhibited a biological action similar to cardiac ANF. This finding supports a possible involvement of ANF in the regulation of both, central and peripheral neuronal activities.

Presence of Conjugated Catecholamines in Rat Brain: A New Method of Analysis of Catecholamine Sulfates

Abstract: A new method of measuring catecholamine (CA) sulfate permitted us to detect its presence in rat brain for the first time. The procedure consisted of separating the CA sulfate from the free CA by alumina adsorption followed by passage through Dowex, and measuring the CA sulfate by a radioenzymatic assay in the presence of a sulfatase. This method permitted demonstration of the presence of dopamine sulfate, and occasionally, of norepinephrine and epinephrine sulfate in the hypothalamus, striatum, and hippocampus of rat brain.

The direct conversion of dopamine 3-0-sulfate to norepinephrine by dopamine-β-hydroxylase

Abstract Dopamine 3-0-sulfate is present in considerable amounts in mammalian plasma and peripheral tissues. Incubation of dopamine 3-0-sulfate (0.1 μmole) with purified bovine dopamine-β-hydroxylase resulted in the formation of free norepinephrine (7.3 × 10−3 μmole). The conversion to norepinephrine was inhibited by 0.6 mM of fusaric acid, an inhibitor of dopamine-β-hydroxylase. The reaction of dopamine 3-0-sulfate with dopamine-β-hydroxylase followed Michaelis-Menten kinetics. The calculated Km was 17 mM, different from the Km for free dopamine (0.1 mM). The incubation medium does not contain any sulfatase activity.

Atrial natriuretic factor partially inhibits the stimulated catecholamine synthesis in superior cervical ganglia of the rat

We examined whether the atrial natriuretic factor (ANF) may affect the function of the peripheral autonomic neurons. ANF was found to inhibit the carbachol-stimulated synthesis of catecholamines from their labelled [3H]tyrosine precursor in an organ suspension of the rat superior cervical ganglia in vitro. This is compatible with the possibility that the previously observed inhibitory action of ANF on sympathetic nervous activity and the presence of immunoreactive ANF in the rat peripheral autonomic ganglia is related to an inhibitory-neuromodulatory role of ANF in the process of ganglionic neurotransmission.

Catecholamine Glucuronidation: An Important Metabolic Pathway for Dopamine in the Rat

Abstract: In the present study, we found that large quantities of dopamine (DA) glucuronide were present in rat cerebrospinal fluid (CSF), plasma, and urine, whereas the glucuronides of norepinephrine (NE) and epinephrine (E) were almost undetectable. The high urinary excretion of DA glucuronide was in a range comparable to that of homovanillic acid (HVA). Sulfates of DA, NE, and E were measurable in all three body fluids, but only in small quantities. The measured DA glucuronide was predominantly of endogenous origin, as the feeding of sucrose instead of routine diet did not reduce the urinary output of DA glucuronide. Adrenalectomy but not peripheral sympathectomy induced by chronic guanethidine injection substantially decreased plasma DA glucuronide concentrations, indicating that the adrenals serve as an important source of endogenous DA glucuronide. The data suggest that glucuronidation constitutes an important metabolic pathway for endogenous DA of central and peripheral origin in rats; this route, however, is exclusive to DA and appears to play a negligible role for NE and E.

Treatment of Severe Orthostatic Hypotension by Metoclopramide

Excerpt The cardiovascular consequences of a deficient release of norepinephrine at nervous terminals are dependent on its balance with some vasodilator and natriuretic substances (bradykinin, some...

Dopamine-Sodium Relationship: Is Dopamine a Part of the Endogenous Natriuretic System?1

A possible role of DA as an endogenous natriuretic hormone was reviewed under three aspects: (1) its excretion in response to saline vs. albumin-induced volume expansion, (2) the origin of urinary free DA and (3) urinary free DA excretion in an unexplained salt-retaining condition, idiopathic edema. We have shown (1) that the urinary free DA excretion increase in response to saline is specifically related to salt and does not occur when the same degree of volume expansion is induced by albumin, (2) that this increase in free DA originates in the kidney and (3) that idiopathic edema patients excrete less free DA than control subjects. It is proposed that free DA originating in the kidney is a rather sal than volume-dependent endogenous natriuretic factor. Its deficiency may contribute to excessive sodium retention in idiopathic edema. However, DA is probably not the single natriuretic hormone but a part of a natriuretic system, components of which are other renal vasodilating and natriuretic substances such as prostaglandins and kallikrein-bradykinin.

Effects of different monoamine oxidase inhibitors on the metabolism of L-dopa in the rat brain

The influence of monoamine oxidases A and B on the metabolism of dopamine or the expanded dopamine pool following L-dopa administration remains unclear. This study found that treatment of Sprague-Dawley rats with monoamine oxidase inhibitors strongly affected L-dopa metabolism in the brain, but the influence varied with each individual inhibitor. In animals pretreated with pargyline or clorgyline, L-dopa administration led to huge accumulations of dopamine and significantly raised central norepinephrine concentrations. In contrast, similar L-dopa injections in deprenyl-pretreated rats caused only a moderate rise in dopamine and no change in norepinephrine. There seems to be little relationship between the degree of monoamine oxidase inhibition and the accumulation of catecholamines and their metabolites in the rat brain. The effects of monoamine oxidase inhibitors on dopamine accumulation appeared to occur outside the catecholaminergic neurons since in the animals pretreated with 6-hydroxydopamine, which decreased significantly the content of brain catecholamines, dopamine accumulation following L-dopa administration still remained considerable. On the other hand, the influence of monoamine oxidase inhibitors on brain norepinephrine concentrations seemed to originate in the noradrenergic neurons because norepinephrine increase was greatly reduced in rats treated with 6-hydroxydopamine but was restored when the treatment with 6-hydroxydopamine was accompanied by desimipramine which specifically protects noradrenergic stores.

Free and conjugated dopamine in pheochromocytoma, primary aldosteronism and essential hypertension.

SUMMARY Since the hypotensive and natrluretic role recently attributed to dopamine (DA) is difficult to test (free DA is usually undetectable in plasma) we measured free and conjugated DA by a newly developed method of hydrolysis of conjugated catecholamlnes in four pheochromocytoma, four primary aldosteronism and 34 essential hypertensive patients subjected to selective venous catheterization or peripheral venous sampling. The 16 control subjects had plasma DA of 0.98 ± 0.1 ng/ml (SE), almost 100% of which was conjugated, and a urinary excretion of 2 ± 03 fig/min of DA, 79% of which was conjugated.Patients with a predominantly norepinephrine-secreting pheochromocytoma had elevated conjugated plasma DA (6 ± 0.S vs 2.5 ± 03 ng/ml in non-pheochromocytoma hypertensive patients) even between paroxysms; in a rare case an alternating DA and epinephrine hypersecretion was detected during predominantly normotensive paroxysms, one of which was associated with the flooding of the peripheral circulation by up to 5.5 ng/ml of free DA.Patients with primary aldosteronism had elevated total plasma DA (3.1 ± 0 3 ng/ml), detectable free DA (0.4 ± 0.2 ng/ml) and an elevated total urinary DA excretion (53 ± 1.5 /ig/min). Following the removal of the aldosteronoma, urinary excretion of total or free DA decreased to normal levels, except in one patient with a bilateral micronodular hyperplasia in whom the hyperaldosteronism persisted after unilateral adrenalectomy. Patients with essential hypertension bad elevated conjugated plasma DA (1.98 ± 03 ng/ml), probably originating in an adrenal outflow of free and conjugated DA, but lower free and total urinary DA excretion than patients with primary aldosteronism (0.19 ± 0.04 vs 0.61 ± 0.01 for free DA and 0.9 ± 0.04 vs 5 3 ± 1.5 Mg/min for total urinary DA). Measurements of conjugated DA, which probably reflects the release of free rapidly conjugated DA, complement the free DA determination in hypertension. Elevated plasma conjugated DA probably mirrors the endogenous autonomous dopamine release in pheochromocytoma and has an adaptive character in primary aldosteronism and essential hypertension. Urinary free and conjugated DA excretion appears to reflect the dopamine modulated natriuresls, modifying the sodium-retaining action of aldosterone.

Circadian Variations of the Urinary Excretion of Catechola-Mines and Electrolytes

Concomitant measurements of circadian variations in the urinary excretion of dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), epinephrine (E) as well as of creatinine, sodium and potassium under controlled dietary conditions during relative physical and emotional rest in 13 volunteers have shown that maximum excretion of all these substances occurred in the afternoon period between 14:30h and 18:00h, and minimum excretion in the morning between 4:00h and 5:00h. The changes were in some cases progressive from one collection period to the other, and synchronized for NE and E. DA and HVA excretions fluctuated from subject to subject. Excretory rhythms of sodium and potassium were found to be similar to those of the catecholamines. This can be explained by diurnal changes in renal blood flow and different renal excretory mechanisms of catecholamines. None of the catecholamines correlated with the urinary volume but urinary NE and E positively correlated with urinary creatinine, urinary NE and E with urinary DA and urinary sodium with urinary E. There are some common patterns in the diurnal rhythms of catecholamines and electrolytes but their interrelationship is different for individual catecholamines.