Deamination of methylamine by semicarbazidesensitive amine oxidase in human umbilical artery and rat aorta

Precious, Elaine; Gunn, Clare E.; Lyles, Geoffrey A.

doi:10.1016/0006-2952(88)90145-1

Cited by 113 publications

(60 citation statements)

References 24 publications

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“…These symptoms are consistent with the scenario of severe systemic hypotension, accompanied by reflex tachycardia, declining cerebral perfusion, and ultimate coma (10 of 35 people suffered light to deep coma). On the basis of the MA-induced prolonged and robust relaxation in LIMA, RA, and RSV blood vessels in our study, one might predict severe hypotension would follow a systemic, high-level MA dose [assuming the MA relaxation occurs in the resistance vessels-a testable hypothesis that is supported by the ubiquitous presence of SSAO activity in human conductance and resistance blood vessels (11,13,23,32,39)]. …”

Section: Implications For Human Health: Pharmacological and Toxicologmentioning

confidence: 79%

“…For example, MA excretion is elevated in rats after the administration of SSAO inhibitors (34) and in humans after the consumption of creatinine, certain fish and seafood, and some fruits and vegetables (38). Moreover, MA is metabolized by vascular homogenates, including the rat aorta and human umbilical artery, to formaldehyde (9,39). Finally, SSAO inhibitors prevent MA toxicity in cultured endothelial cells (47).…”

mentioning

confidence: 99%

“…The copper-containing SSAOs share common features including insensitivity to MAO inhibitors (e.g., clorgyline, deprenyl), preference for aliphatic amines and the aromatic benzylamine, and inhibition by carbonylcontaining compounds, such as semicarbazide, for which the most current name is derived (33,47). SSAO activity is present in all mammalian cardiovascular tissues tested, including plasma/serum, the aorta, and the heart with the most concentrated SSAO activity present in the mammalian aorta, including those of the human and rat (11,13,14,32,33,37,39,44). This high level of SSAO activity in the cardiovascular tissues implies functionality, although a specific function for the SSAO enzyme has yet to be established (7,33,51).…”

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confidence: 99%

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Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide

Conklin¹,

Cowley²,

Wiechmann

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide. Am J Physiol Heart Circ Physiol 286: H667-H676, 2004; 10.1152/ajpheart.00690. 2003.-It is hypothesized that methylamine (MA) and semicarbazidesensitive amine oxidase (SSAO) activity are involved in the cardiovascular complications in human diabetics. To test this, we 1) determined the acute vasoactive effects of MA (1-1,000 mol/l) in uncontracted and norepinephrine (NE; 1 mol/l)-precontracted human blood vessels used for coronary artery bypass grafts [left internal mammary artery (LIMA), radial artery (RA), and right saphenous vein (RSV)]; 2) tested whether MA effects in LIMA and RSV were dependent on SSAO activity using the SSAO inhibitor semicarbazide (1 mmol/l, 15 min); 3) determined the effects of MA metabolites formaldehyde and hydrogen peroxide in LIMA and RSV; 4) tested whether the MA response was nitric oxide, prostaglandin, or hyperpolarization dependent; 5) measured the LIMA and RSV cGMP levels after MA exposure; and 6) quantified SSAO activity in LIMA, RA, and RSV. In NE-precontracted vessels, MA stimulated a biphasic response in RA and RSV (rapid contraction followed by prolonged relaxation) and dominant relaxation in LIMA (mean Ϯ SE, %relax-ation: 55.4 Ϯ 3.9, n ϭ 30). The MA-induced relaxation in LIMA was repeatable, nontoxic, and age independent. Semicarbazide significantly blocked MA-induced relaxation (%inhibition: 82.5 Ϯ 4.8, n ϭ 7) and SSAO activity (%inhibition: 98.1 Ϯ 1.3, n ϭ 26) in LIMA. Formaldehyde (%relaxation: 37.3 Ϯ 18.6, n ϭ 3) and H 2O2 (%relax-ation: 55.6 Ϯ 9.0, n ϭ 9) at 1 mmol/l relaxed NE-precontracted LIMA comparable with MA. MA-induced relaxation in LIMA was nitric oxide, prostaglandin, and possibly cGMP independent and blocked by hyperpolarization. We conclude that vascular SSAO activity may convert endogenous amines, like MA, to vasoactive metabolites. amine metabolism; coronary artery bypass grafts; diabetes; H2O2 A CURRENT HYPOTHESIS STATES that chronic methylamine (MA) exposure induces vascular injury and promotes vascular disease, including atherosclerosis, in humans via semicarbazidesensitive amine oxidase-mediated (SSAO) metabolism of MA to injurious metabolites: formaldehyde, H 2 O 2 , and ammonia (NH 3 ) (19, 50-52). Recent clinical and experimental studies support such a relationship. Altered plasma MA levels, MA excretion, and elevated plasma SSAO activity are present in human diseases associated with chronic vascular pathology [e.g., diabetes mellitus and uremia (Refs. 3,5,6,27, and 49; for reviews, see Refs. 19 and 51)]. In the case of Type I diabetes, SSAO plasma levels increase at the onset of disease (6) and plasma SSAO activity positively correlates with the amount of glycosylated hemoglobin, an indicator of the severity of complications in human diabetics (5, 43). Similarly, plasma SSAO activity is elevated within 2 wk after streptozotocin-induced diabetes in rats (22). Thus much circumstantial evidence link...

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Section: Implications For Human Health: Pharmacological and Toxicologmentioning

confidence: 79%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide

Conklin¹,

Cowley²,

Wiechmann

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…Nevertheless, although MET has been known from many years, its physiopathological role has still not been completely clari®ed. It is known that the urinary excretion of MET is enhanced in particular physiological conditions that are characterized by an increase in creatine elimination, including pregnancy, parturition and muscular exertion (Dar et al, 1985;Precious et al, 1988). It has also been reported that the amine increases in typhoid fever, diabetes, hepatic or renal insu ciency where it is suspected of generating a variety of central or peripheral e ects.…”

Section: Introductionmentioning

confidence: 99%

Methylamine and benzylamine induced hypophagia in mice: Modulation by semicarbazide‐sensitive benzylamine oxidase inhibitors and aODN towards Kv1.1 channels

Pirisino¹,

Ghelardini²,

Banchelli³

et al. 2001

British J Pharmacology

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1 In starved mice, the anorectic activity of methylamine (MET) and benzylamine (BZ), both substrates of semicarbazide-sensitive benzylamine oxidases (Bz-SSAO), was compared with that of the potassium channel blocking agents charybdotoxin (ChTX), tetraethylammonium (TEA), gliquidone (GLI), ammonium chloride ( 4 Antisense oligodeoxyribonucleotides (aODN) to Kv1.1 potassium channels abolished the e ect of BZ and TEA, but was ine ective in reducing the activity of MET and other compounds. 5 These results suggest that MET is endowed with peculiar hypophagic e ects at dosage levels that are not able to a ect gross behaviour in mice. The e ect of MET, di erently from BZ, seems unrelated to an increase in the central release of monoaminergic mediators, as well as to a Kv1.1 blocking activity. Through a reduction of the endogenous breakdown of MET, Bz-SSAO inhibitors enhance the central pharmacological activity of this amine.

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“…Homogenates of blood vessels have been widely used to examine the biochemical properties of this enzyme activity (Lewinsohn et al, 1978;Clarke et al, 1982;Precious et al, 1988;Elliott et al, 1989b).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of amines in the isolated perfused mesenteric arterial bed of the rat

Elliott

Callingham

Sharman

1989

British J Pharmacology

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1 Semicarbazide-sensitive amine oxidase (SSAO) activity has been demonstrated in the isolated mesenteric arterial bed of the rat in vitro by studying the metabolism of benzylamine (Bz) and tyramine (Tyr) added to the perfusing fluid. 2 Pretreatment of rats with (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine (MDL72145), a potent inhibitor of SSAO in rat mesenteric blood vessels, reduced the amount of metabolites, following the addition of Bz (25 uM) or Tyr (100pM) to the perfusing fluid, by 83% and 52% respec-' tively. Inactivation of monoamine oxidase type A (MAO-A) by the addition of clorgyline (10pM) to the perfusing fluid, had little effect on the appearance of metabolites from Tyr. 3 The presence of 3 UM cocaine in the perfusing fluid increased the amount of metabolites produced from Tyr. 4 The metabolites of Tyr appearing in the perfusion fluid from control preparations were 85% p-hydroxyphenylacetic acid and the remainder consisted of a mixture of phydroxyphenylacetaldehyde and, possibly, p-hydroxyphenylethanol. 5 The metabolism of Tyr by homogenates of the rat mesenteric vascular bed was carried out by SSAO (60%) and MAO-A (40%) with very little contribution from MAO-B. Homogenates from rats pretreated with MDL 72145 showed metabolism of Tyr by MAO-A only. 6 These data indicate that SSAO is capable of metabolizing amines present in the fluid perfusing blood vessels to metabolites that are readily released. Histochemical evidence has shown that whereas MAO-A is present in the mitochondria of smooth muscle cells and nerve endings, SSAO is located in the plasma membrane of the smooth muscle cells. This subcellular distribution may explain the differences found between metabolites released from intact vessels and the metabolism seen in homogenates. The identity of the Tyr metabolizing activity in intact vessels that is resistant to both MDL 72145 and clorgyline remains to be determined. IntroductionRat blood vessels possess an amine oxidase activity capable of metabolising tyramine (Tyr), which has different properties from monoamine oxidase (MAO; EC 1.4.3.4) enzymes (Coquil et al., 1973 Callingham & Barrand 1987, for review). SSAO has been shown to reside in the plasma membrane of vascular smooth muscle cells (Wibo et al., 1980;Lyles & Singh, 1985).Homogenates of blood vessels have been widely used to examine the biochemical properties of this enzyme activity (Lewinsohn et al., 1978;Clarke et al., 1982;Precious et al., 1988;Elliott et al., 1989b).The preferred substrate appears to be benzylamine (Bz) but a number of aromatic and aliphatic amines also have been shown to be substrates. In spite of all the work done with homogenates, this enzyme has not been studied in intact blood vessels of the rat and its physiological significance is poorly understood.Studies with intact rat caudal artery confirm the long held view that neuronal uptake mechanisms are important for the inactivation of noradrenaline. Catechol-O-methyltransferase and extraneuronal uptake make a more significant contribution when the ...

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Deamination of methylamine by semicarbazidesensitive amine oxidase in human umbilical artery and rat aorta

Cited by 113 publications

References 24 publications

Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide

Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide

Methylamine and benzylamine induced hypophagia in mice: Modulation by semicarbazide‐sensitive benzylamine oxidase inhibitors and aODN towards Kv1.1 channels

Metabolism of amines in the isolated perfused mesenteric arterial bed of the rat

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