Inhibition of Dopamine- -Hydroxylase by Hydralazine

Liu, Tsan Z.; Shen, Junyang; Löken, Hans F.

doi:10.3181/00379727-145-37796

Cited by 13 publications

(4 citation statements)

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“…Furthermore, this result seems to exclude the possibility that Hyd might interfere with the reuptake of purines in nerve terminals, as dipyridamole does (Stafford, 1966 (Liu, Shen & Loken, 1974). Never-,ctional release per shock during a given theless, the prejunctional negative effect of Hyd inhilation (SX) and the first period (S1).…”

Section: Solutions Usedmentioning

confidence: 99%

Hydralazine: Effect on the Outflow of Noradrenaline and Mechanical Responses Evoked by Sympathetic Nerve Stimulation of the Rat Tail Artery

Chevillard

Mathieu

Saiag

et al. 1980

British J Pharmacology

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1 The effects of hydralazine on the vasoconstrictor responses to field stimulation of sympathetic nerves were studied in the isolated proximal segments of the rat tail artery. Vasoconstrictor responses to transmural stimulation were depressed by superfusion of hydralazine (0.3, 3 and 30pM) in a concentration-dependent manner. The inhibition appeared slowly and was not easily reversed by washing.2 Hydralazine (30 nm, 0.3 and 3 gM) reduced the stimulation-induced overflow of tritium from proximal and distal segments of the tail artery labelled with [3H]-noradrenaline in a concentrationdependent manner. This phenomenon appeared rapidly and was easily reversed by washing. 3 Theophylline (0.5 mM) did not affect the inhibitory effect of hydralazine on the stimulation-induced tritium efflux from the distal segment of the rat tail artery. 4 The present results indicate that hydralazine has, in addition to its action on vascular smooth muscle, a very marked effect on sympathetic nerve terminals. The mechanism of this presynaptic inhibition appears to be different from the postsynaptic effect, in view of the much shorter delay, the shape of the dose-effect curve, and the lack of interaction with theophylline.

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Section: Solutions Usedmentioning

confidence: 99%

Hydralazine: Effect on the Outflow of Noradrenaline and Mechanical Responses Evoked by Sympathetic Nerve Stimulation of the Rat Tail Artery

Chevillard

Mathieu

Saiag

et al. 1980

British J Pharmacology

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“…On some it acts in a reversible fashion as a chelator and no specific binding occurs, e.g. prolyl hydroxylase (Bhatnagar et al, 1972) and dopamine-/Jhydroxylase (Liu et al, 1974). With lysyl oxidase, inhibition is irreversible and enzyme activity cannot be restored by dialysis in the presence of either the putative cofactor pyridoxal or Cu2+ (Numata et al, 1981).…”

Section: Resultsmentioning

confidence: 99%

The interaction of hydralazine with a semicarbazide-sensitive amine oxidase in brown adipose tissue of the rat. Its use as a radioactive ligand for the enzyme

Barrand¹,

Callingham²

1985

Biochemical Journal

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Hydralazine is a potent irreversible inhibitor of the semicarbazide-sensitive amine oxidase (SSAO) found in brown fat. Initially it may act on the enzyme as a competitive inhibitor, but irreversible inhibition occurs rapidly in a concentration- and temperature-dependent manner. The presence of primary amines known to be substrates for the enzyme, but not of secondary amines, which are not metabolized by SSAO, diminishes this rate of inactivation, whereas removal of O2 is without effect. The kinetic pattern of inactivation of SSAO by hydralazine is consistent with an active-site-directed site-saturable binding followed by the development of an irreversible enzyme-inhibitor complex. [3H]Hydralazine, used as an affinity label for SSAO, shows saturable binding to brown-fat membranes. This binding is inhibited by other inhibitors of SSAO. The rate of binding to membrane pellets containing SSAO is not affected by substrates for the enzyme. However, if solubilized partially purified SSAO preparations are used instead, the rate of binding is lowered in the presence of the SSAO substrate benzylamine. 3H-labelled material solubilized from [3H]hydralazine-treated membrane pellets by Triton X-100 at that detergent/protein ratio which releases SSAO from membranes shows the same gel-filtration characteristics as SSAO and appears by lentil lectin-agarose affinity chromatography to contain similar carbohydrate moieties. 3H-labelled material, partially purified by gel filtration and affinity chromatography, produces predominantly a single band of radioactivity on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The position of this band corresponds to an Mr of about 94 000, almost exactly half the Mr already estimated for the functional unit of SSAO. Radiolabelled hydralazine may thus be used as a label for purified SSAO, but it is not specific enough to be suitable as a ligand in vivo.

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“…However, hydralazine is not a potent vasodilator and its effect in inhibiting the conversion of dopamine to noradrenaline may contribute to its antihypertensive activity. Liu, Shen & Loken (1974) showed that hydralazine inhibited a preparation of dopamine-fi-hydroxylase extracted from the bovine adrenal gland; this inhibition was attributed to chelation by hydralazine of copper ions which inactivate endogenous inhibitors of the enzyme. In the present study, a concentration-dependent inhibition of the conversion of (3H)-dopamine to (3H)-noradrenaline by hydralazine was demonstrated in an intact tissue, namely, rat isolated atria.…”

Section: Discussionmentioning

confidence: 99%

“…Hydralazine has been shown to inhibit dopamine-P-hydroxylase in an extract prepared from bovine adrenal glands (Liu, Shen & Loken, 1974). The aim of the present study was to evaluate the effect of hydralazine on the conversion of dopamine to noradrenaline in intact rat atria, in uitro and in uivo, in order to determine whether this effect of hydralazine may have some relevance to its antihypertensive action.…”

Section: Introductionmentioning

confidence: 99%

INHIBITION BY HYDRALAZINE OF THE CONVERSION OF DOPAMINE TO NORADRENALINE IN RAT ATRIA IN VITRO AND IN VIVO

Songkittiguna

Majewski

Rand

1980

Clin Exp Pharma Physio

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1. Hydralazine (10 to 2000 microgramol/l) produced a concentration-dependent inhibition of the conversion of (3H)-dopamine to (3H)-noradrenaline in rat isolated atria. 2. In rats treated with hydralazine (2 mg/kg, i.p.), there was an inhibition of the conversion of (3H)-dopamine to (3)-noradrenaline in the intact artia in vivo. 3. Hydralazine treatment may result in the appearance of dopamine as a significant co-transmitter in noradrenergic nerves, and this may contribute to the antihypertensive effect of hydralazine.

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Inhibition of Dopamine- -Hydroxylase by Hydralazine

Cited by 13 publications

References 0 publications

Hydralazine: Effect on the Outflow of Noradrenaline and Mechanical Responses Evoked by Sympathetic Nerve Stimulation of the Rat Tail Artery

Hydralazine: Effect on the Outflow of Noradrenaline and Mechanical Responses Evoked by Sympathetic Nerve Stimulation of the Rat Tail Artery

The interaction of hydralazine with a semicarbazide-sensitive amine oxidase in brown adipose tissue of the rat. Its use as a radioactive ligand for the enzyme

INHIBITION BY HYDRALAZINE OF THE CONVERSION OF DOPAMINE TO NORADRENALINE IN RAT ATRIA IN VITRO AND IN VIVO

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