The presence of phenylethanolamine-N-methyltransferase in cerebral microvessel and endothelial cultures

Spatz, Maria; Nagatsu, Ikuko; Maruki, Chikashi; Yoshida, Masami; Kondo, Yukari; Bembry, J.

doi:10.1016/0006-8993(82)90663-1

Cited by 19 publications

(9 citation statements)

References 10 publications

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“…The observations presented here provide the first evidence of 5-HT synthesis in the extraneuronal cells of the central nervous system, besides the previously reported presence of cerebrovascular endothelial phenylethanolamine-N-methyltransferase (PNMT), the catecholamine-synthesizing enzyme which converts norepinephrine to epinephrine (Spatz et al, 1982). Although the physiological role of the formed 5-HT is unknown, its known vasoactive properties suggest that it might be involved in the regulation of cerebral microcirculation and/ or in the regulation of the events occurring on the BBB level.…”

Section: -Htsupporting

confidence: 58%

Cerebrovascular Endothelial Cell Culture: Metabolism and Synthesis of 5‐Hydroxytryptamine

Maruki

Spatz

Ueki

et al. 1984

Journal of Neurochemistry

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The presence of 5-hydroxytryptamine was investigated in cultured and propagated cerebrovascular endothelium using immunohistochemistry and high pressure liquid chromatography. These studies demonstrate that the endothelium has the ability to take up and metabolize 5-hydroxytryptamine as well as to synthesize this amine from its precursor L-tryptophan, thus providing evidence for extraneural synthesis of 5-hydroxytryptamine in the central nervous system.

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Section: -Htsupporting

confidence: 58%

Cerebrovascular Endothelial Cell Culture: Metabolism and Synthesis of 5‐Hydroxytryptamine

Maruki

Spatz

Ueki

et al. 1984

Journal of Neurochemistry

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“…30 In addition to circulating EPI, EPI also is synthesized in endothelial cells of blood vessels. 18 Thus, EPI may regulate vascular tone and BP locally. When sympathetic innervation was inhibited by ganglionic blockade with HEX in the present study, BP decreased in both KO and WT mice, but the BP decrease was significantly less in KO mice.…”

Section: Discussionmentioning

confidence: 99%

“…Third, EPI synthesis is concentrated in the adrenal medulla but also is present in many adult tissues outside the adrenal such as heart [15][16][17] and blood vessels. 18 These peripheral tissues might make enough EPI to tonically stimulate adrenergic receptors locally because EPI is a potent agonist of adrenergic receptors, especially the ␤ 2 -adrenergic receptor, for which it has a much higher affinity than any other known endogenous compound. 19 Fourth, although several PNMT inhibitors currently are available to block EPI synthesis in vivo, most PNMT inhibitors also inhibit other catecholamine processes such as monoamine oxidase and ␣ 2 receptors.…”

Section: Clinical Perspective P 1031mentioning

confidence: 99%

Epinephrine Is Required for Normal Cardiovascular Responses to Stress in the Phenylethanolamine N-Methyltransferase Knockout Mouse

Bao

Liu

et al. 2007

Circulation

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Background-Epinephrine (EPI) is an important neurotransmitter and hormone. Its role in regulating cardiovascularfunction at rest and with stress is unclear, however. Methods and Results-An epinephrine-deficient mouse model was generated in which the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase was knocked out (KO). Blood pressure and heart rate were monitored by telemetry at rest and during graded treadmill exercise. Cardiac structure and function were evaluated by echocardiography in mice under 1 of 2 conditions: unstressed and lightly anesthetized or restrained and awake. In KO mice, resting cardiovascular function, including blood pressure, heart rate, and cardiac output, was the same as that in wild-type mice, and the basal norepinephrine plasma level was normal. However, inhibition of sympathetic innervation with the ganglion blocker hexamethonium caused a 54% smaller decrease in blood pressure in KO mice, and treadmill exercise caused an 11% higher increase in blood pressure, both suggesting impaired vasodilation in KO mice. Interestingly, phenylethanolamine N-methyltransferase KO did not change the heart rate response to ganglionic blockade and exercise. By echocardiography, KO mice had an increased ratio of left ventricular posterior wall thickness to internal dimensions but did not have cardiac hypertrophy, suggesting concentric remodeling in the KO heart. Finally, in restrained, awake KO mice, heart rate and ejection fraction remained normal, but cardiac output was significantly reduced because of diminished end-diastolic volume. Conclusion-Our data suggest that epinephrine is required for normal blood pressure and cardiac filling responses to stress but is not required for tachycardia during stress or normal cardiovascular function at rest.

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“…The demonstration of this enzyme in the extraneuronal compartment and partic ularly in the cerebrovascular endothelium suggests that the cerebral microvessels are capable of synthesizing adrenaline (Ad) from noradrenaline (NAd) (1). There are few reports on the cerebrovascular reactivities to N-methylated catecholamines.…”

mentioning

confidence: 99%

“…Both circulating NAd and NAd released from nerve terminals in the blood vessels may be converted to Ad in cerebral vessels (1). Indeed, inhibitors of phenylethanolamine-N-methyltransferase de creased the systemic blood pressure of the rat (2-4).…”

mentioning

confidence: 99%

Cerebrovascular Reactivities to N-Methylated Catecholamines in Humans, Monkeys and Dogs

Usui

Shirahase

Kurahashi

1990

Japanese Journal of Pharmacology

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Abstract-A comparison was made of the cerebrovascular responses of humans, monkeys and dogs to noradrenaline (NAd) and dopamine (DA) as well as to their N-methylated derivatives, adrenaline (Ad) and N-methyl dopamine (methyl DA). The present experiments demonstrated that N-methylation of both NAd and DA enhanced the contractile responses of these agents in human cerebral arteries, while only N-methylation of DA enhanced the contraction of monkey cerebral arteries, and such an enhancement was not seen in dog cerebral arteries.

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The presence of phenylethanolamine-N-methyltransferase in cerebral microvessel and endothelial cultures

Cited by 19 publications

References 10 publications

Cerebrovascular Endothelial Cell Culture: Metabolism and Synthesis of 5‐Hydroxytryptamine

Cerebrovascular Endothelial Cell Culture: Metabolism and Synthesis of 5‐Hydroxytryptamine

Epinephrine Is Required for Normal Cardiovascular Responses to Stress in the Phenylethanolamine N-Methyltransferase Knockout Mouse

Cerebrovascular Reactivities to N-Methylated Catecholamines in Humans, Monkeys and Dogs

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