Characterisation, Localisation and Regulation of Catecholamine Synthesizing Enzymes

Goldstein, Menek; Anagnoste, B; Freedman, Lewis S.; Roffman, Mark; Ebstein, Richard P.; Park, Dong H.; Fuxé, Kjell; Hökfelt, Tomas

doi:10.1016/b978-0-08-017922-3.50010-1

Cited by 45 publications

(19 citation statements)

References 25 publications

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“…The prodrug also increases aldosterone production as previously reported but the time course of the changes in sodium excretion and the lack of effect on urinary potassium excretion suggest that the antinatriuresis occurs independently of the known actions of aldosterone [6,9]. Both the enzymes required for 5-HT synthesis from glu-5-HTP, yGT and LAAD, are highly concentrated in the proximal tubular cells of the kidney [3,10] and the high urinary levels of 5-HT would indicate that 5-HT is probably formed in the renal tubules and then excreted. That 5-HT is produced intrarenally is further supported by our recently reported findings that the marked increases in urinary excretion of 5-HT occur without significant changes in circulating 5-HT [1 1].…”

Section: Discussionsupporting

confidence: 50%

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

Freestone

Samson

et al. 1994

Brit J Clinical Pharma

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1 The effects of inhibition of peripheral aromatic L-amino acid decarboxylase during infusion of the relatively renally selective 5-hydroxytryptamine (5-HT) prodrug, y-L-glutamyl-5-hydroxy-L-tryptophan , were examined in eight healthy male subjects in a randomised, placebo-controlled, cross-over study. 2 Each subject received oral carbidopa (100 mg) or placebo followed, 1 h later, by a 60 min intravenous infusion of glu-5-HTP (16.6 jg kg-1 min-') or placebo.3 After administration of glu-5-HTP, cumulative urinary excretion of 5-HT was 430-fold greater than that after placebo, and was associated with a period of sodium retention. 4 Pretreatment with carbidopa substantially attenuated the increase in 5-HT excretion after glu-5-HTP and abolished its antinatriuretic effect. 5 These results are in keeping with the proposition that the antinatriuretic action of glu-5-HTP is dependent on its decarboxylation to 5-HT. 5-hydroxytryptamine sodium excretion ale y-L-glutamyl-5-hydroxy-L-tryptophan dosteroneThe first step in the biosynthesis of 5-hydroxytryptamine (5-HT; serotonin) involves the hydroxylation of the essential amino acid L-tryptophan to 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan-5-hydroxylase. 5-HTP is decarboxylated by aromatic L-amino acid decarboxylase (LAAD) to 5-HT. The latter is degraded primarily by monoamine oxidase to produce 5-hydroxyindoleacetic acid (5-HIAA) which is the major catabolic and excretory product of 5-HT metabolism. All these enzymes are present in renal tissue, suggesting that the kidney might have the capacity to synthesise and degrade 5-HT locally [1,2]. The enzyme y-glutamyl transferase (yGT) is also present in high concentrations and the kidney is highly active in the uptake and metabolism of y-glutamyl derivatives of amino acids [3,4]. We previously demonstrated marked increases in urinary 5-HT excretion after infusion of the 5-HT prodrug, y-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP), in keeping with intrarenal synthesis of 5-HT following the conversion of glu-5-HTP to 5-HTP by yGT and its subsequent decarboxylation by renal LAAD to 5-HT [5,6]. Glu-5-HTP was relatively more selective for the kidney than 5-HTP. It reduced urinary sodium excretion without significant alterations in renal haemodynamics and this was due, presumably, to intrarenally generated 5-HT.The present study was designed to investigate whether carbidopa, a peripheral inhibitor of LAAD [7], blocks the formation of 5-HT from glu-5-HTP and interferes with the actions of glu-5-HTP in normal volunteers. MethodsEight male volunteers, age range 18-39 years (mean 28 years) and weighing 59.9-80.9 kg (mean 69.0 kg),

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Section: Discussionsupporting

confidence: 50%

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

Freestone

Samson

et al. 1994

Brit J Clinical Pharma

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Section: Methodsmentioning

confidence: 99%

“…Antisera to highly purified APP and highly purified porcine VIP were raised in rabbits as will be described elsewhere. The antisera to the catecholamine-synthesizing enzymes tyrosine hydroxylase [TyrOHase; L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and dopamine ,f3hydroxylase [Df3OHase; 3,4-dihydroxyphenylethylamine, ascorbate: oxygen oxidoreductase ( , ( hydroxylating), EC 1.14.17.1], purified from rat pheochromocytoma and cow adrenal glands, respectively, have been described (17,18).Male guinea pigs (body weight, 200-300 g) and adult cats of both sexes (body weight 2-3 kg) were used. In two cats, vinblastine sulphate (Sigma) (0.1% in 0.9% NaCl) was locally applied to the superior cervical and the L7 sympathetic ganglia 24 hr prior to sacrifice.…”

mentioning

confidence: 99%

Organizational principles in the peripheral sympathetic nervous system: Subdivision by coexisting peptides (somatostatin-, avian pancreatic polypeptide-, and vasoactive intestinal polypeptide-like immunoreactive materials

Lundberg

Hökfelt

Änggård

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

168

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Sympathetic ganglia and some peripheral tissues of adult guinea pig and cat were analyzed by the indirect immunofluorescence technique with antisera to catecholamine-synthesizing enzymes and some peptides. In the guinea pig, noradrenergic neurons could be subdivided into three populations containing respectively (i) somatostatin-like immunoreactive material, (ii) avian pancreatic polypeptide (APP)-like immunoreactive material, and (iii) apparently only noradrenaline (NA; norepinephrine). A fourth population of sympathetic neurons was nonadrenergic and contained vasoactive intestinal polypeptide (VIP)-immunoreactive material. In the cat many noradrenergic neurons with APP and some without this peptide were seen, but no somatostatin-immunoreactive neurons were observed. Also a population of non-adrenergic, presumably cholinergic, neurons containing a VIP-like peptide was observed. These neuron, populations seemed to innervate different tissues with some target specificity.For example, in the nasal mucosa ofthe cat, nerves containing NA/ APP-like immunoreactive material (called NA/APP nerves) were found around small arteries and arterioles, whereas venules and sinusoids were surrounded by nerves containing only NA (called NA nerves). Also in the submandibular salivary gland of the cat, the NA/APP nerves surrounded arteries and drterioles, whereas NA nerves were seen in relation to acini and ducts. The sympathetic (cholinergic) VIP-containing neurons innervated blood vessels and exocrine tissue in the cat sweat glands. In the coeliac-superior mesenteric ganglion complex of the guinea pig and cat, a dense network of VIP-immunoreactive fibers was seen preferentially around noradrenergic ganglionic cell bodies lacking APP-immunoreactive material. Thus, adult peripheral sympathetic neurons can be subdivided into several categories on the basis of specific peptides. These subdivisions may innervate specific targets and may receive peptide-specific neuronal inputs.Classically the peripheral autonomic nervous system can be subdivided into the sympathetic and the parasympathetic portions (1, 2). The enteric nerves have been considered to represent a separate division (3). The principal transmitter in the sympathetic division is noradrenaline (NA), as discovered by von Euler (4). However, a small population of sympathetic nerves supply sweat glands (5, 6) and skeletal muscle vessels and are cholinergic (7).During recent years, an extensive distribution ofpeptides in peripheral neurons has been identified (8-10). Further analysis has revealed-that some of these peptides coexist with classical transmitters in sympathetic neurons. Thus, some peripheral noradrenergic cell bodies in sympathetic ganglia of the guinea pig, particularly prevertebral ganglia, contain a somatostatinlike peptide (11). An avian pancreatic polypeptide (APP)-like peptide has been demonstrated in a population of peripheral noradrenaline neurons (12). Finally, the acetylcholine (AcCho) esterase-rich, presumably cholinergic, neurons in sympathetic g...

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“…Its origin is uncertain because there is insufficient dopamine in plasma to provide the amount excreted, suggesting that intrarenal dopamine formation is the most likely source (Alexander, Gill, Yamabe, Lovenberg & Keiser, 1974). Since dopamine in the sympathetic nervous system and the brain is derived from DOPA, and the enzyme aromatic amino acid decarboxylase is present in renal tubules (Goldstein, Fuxe & Hokfelt, 1972), the most probable precursor for renal dopamine formation is circulating DOPA. Existing assays are not sufficiently sensitive to determinine normal circulating levels of DOPA in human plasma.…”

Section: Introductionmentioning

confidence: 99%

A specific radioenzymatic assay for dihydroxyphenylalanine (DOPA). Plasma dopa may be the precursor of urine free dopamine.

Brown¹,

Dollery²

1981

Brit J Clinical Pharma

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1 A sensitive radioenzymatic assay was developed, in which DOPA is enzymatically decarboxylated to dopamine and the latter converted to [:H]-methoxytryamine in the presence of [:3H]-S-adenosyl-Lmethionine and catechol-o-methyltransferase. 2 The assay was specific for DOPA, and was sensitive to 50 pg/ml.3 Endogen6us DOPA was found to be present in the plasma of eight human volunteers at a concentration of 10.46 + 2.42 nmol/l. 4 Simultaneous urine collections in the same subjects showed a free dopamine excretion of 68.88 ± 17.70 nmol/h. There was a significant correlation (P < 0.01) between plasma DOPA concentration and urine free dopamine excretion (r = 0.84). 5 After the oral administration of 250 mg levodopa, plasma DOPA and urine dopamine both increased by a similar proportion (98 ± 8.4-fold, and 93.4 ± 6.9-fold respectively). These compare with an increase in plasma dopamine of only 26 ± 15-fold (P<0.01).6 Following the oral dose of DOPA, the increase in plasma DOPA, but not plasma dopamine, could account for the increase in urine dopamine. The calculated clearance of plasma DOPA by renal decarboxylation to dopamine was 114 + 20 ml/min. 7 This is not significantly different from the apparent clearance of endogenous DOPA by renal decarboxylation to dopamine, and suggests that there is adequate renal decarboxylase activity for DOPA to be the precursor for renal dopamine formation.

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Characterisation, Localisation and Regulation of Catecholamine Synthesizing Enzymes

Cited by 45 publications

References 25 publications

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

Organizational principles in the peripheral sympathetic nervous system: Subdivision by coexisting peptides (somatostatin-, avian pancreatic polypeptide-, and vasoactive intestinal polypeptide-like immunoreactive materials

A specific radioenzymatic assay for dihydroxyphenylalanine (DOPA). Plasma dopa may be the precursor of urine free dopamine.

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