Monoamine oxidase activity of shistosoma mansoni

Nimmon-Smith, R.H.; Raison, C. G.

doi:10.1016/0010-406x(68)90992-4

Cited by 35 publications

(8 citation statements)

References 39 publications

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“…This internal transport system is believed to mediate the re-uptake of neuronally released 5HT and may also sequester excess hostderived amine that would otherwise accumulate to toxic levels. In addition there is biochemical evidence that serotonin is metabolized to a 5-hydroxyindole acetic acid (5-HIAA)-like substance in H. diminuta (Ribeiro & Webb, 1984) and S. mansoni (Nimmo- Smith & Raison, 1968), presumably through the activity of a monoamine oxidase (MAO). Thus, flatworms appear to have mechanisms in place for the internalization and degradation of 5HT, not unlike those seen in other organisms.…”

Section: Ht Biosynthesis Transport and Inactivationmentioning

confidence: 99%

Classical transmitters and their receptors in flatworms

2006

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The flatworm nervous system employs a wide repertoire of neuroactive substances, including small chemical messengers, the so called classical transmitters, and several types of neuropeptides. A large body of research accumulated over four decades has provided a wealth of information on the tissue localization and effects of these substances, their biochemistry and, recently, their molecular modes of action in all major classes of flatworms. This evidence will be reviewed, with particular emphasis on the small (classical) transmitters and the receptors that mediate their effects. One of the themes that will emerge from this discussion is that classical transmitters regulate core activities such as movement, metabolism and transport, and thus are essential for survival of the organism. In addition, the evidence shows that flatworms have multiple neurotransmitter receptors, many with unusual pharmacological features, which make them particularly attractive as drug targets. Understanding the molecular basis of these distinctive properties, and developing new, more specific receptor agonists and antagonists will undoubtedly become a major challenge in future research.

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Section: Ht Biosynthesis Transport and Inactivationmentioning

confidence: 99%

Classical transmitters and their receptors in flatworms

2006

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“…Reciprocally some compounds that are active against Sm.5HTR L show poor efficacy in ex vivo worm movement assays, perhaps due to pharmacokinetic variables such as whether the ligand is free to diffuse through the parasite tegument, is a substrate for active transporters such as SERT (Patocka and Ribeiro, 2007), or is degraded by worm enzymes such as monoamine oxidase (Nimmo-Smith and Raison, 1968). These variables may account for the right shifted dose response curves of serotonin in cell based cAMP assays (Fig.…”

Section: Discussionmentioning

confidence: 99%

Structure-activity profiling of alkaloid natural product pharmacophores against a Schistosoma serotonin receptor

Marchant

Harding

Chan

2018

International Journal for Parasitology: Drugs and Drug Resistan

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Serotonin (5-HT) is an important regulator of numerous aspects of flatworm biology, ranging from neuromuscular function to sexual maturation and egg laying. In the parasitic blood fluke Schistosoma mansoni, 5-HT targets several G-protein coupled receptors (GPCRs), one of which has been demonstrated to couple to cAMP and regulate parasite movement. This receptor, Sm.5HTRL, has been successfully co-expressed in mammalian cells alongside a luminescent cAMP-biosensor, enabling pharmacological profiling for candidate anti-schistosomal drugs. Here, we have utilized this assay to perform structure-activity investigations of 143 compounds containing previously identified alkaloid natural product pharmacophores (tryptamines, aporphines and protoberberines) shown to regulate Sm.5HTRL. These experiments mapped regions of the tryptamine pharmacophore amenable and intolerant to substitution, highlighting differences relative to orthologous mammalian 5-HT receptors. Potent Sm.5HTRL antagonists were identified, and the efficacy of these compounds were evaluated against live adult parasites cultured ex vivo. Such structure-activity profiling, characterizing the effect of various modifications to these core ring systems on Sm.5HTRL responses, provides greater understanding of pharmacophores selective for this target to aid future drug development efforts.

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“…MAO activity of A. galli appears to be thermolabile, an increase in incubation temperature by 5° above optimum inactivating the enzyme by over 80%. S. mansoni MAO appears to be more stable, 15 and 40% inactivation being observed after preincubation at 50°C for 20 min using tryptamine and 5-HT as the substrate (NIMMO-SMITH & RAISON, 1968). Mammalian MAO is comparatively more stable than MAO from parasites as rat heart (SEN et al, 1968) can withstand incubation at an elevated temperature for longer.…”

Section: Discussionmentioning

confidence: 99%

“…Recently our attention has been centred on the metabolism of catecholamines and indolealkylamines because of their role as putative neuromuscular transmitters (GIANUTSOS & BENNETT, 1977) and in regulating carbohydrate metabolism in parasitic helminths (MANSOUR et al, 1960;MANSOUR & MANSOUR, 1962). Monoamine oxidase (Monoamine: O 2 oxidoreductase (deaminating), EC 1, 4, 3, 4), an enzyme responsible for the catabolism of biogenic monoamines by oxidative deamination in vertebrates (HORITA, 1967;COLLINS & SANDLER, 1971) has alsp been reported in a few parasitic helminths, namely, Schistosoma mansoni (see NIMMO-SMITH & RAISON, 1968), Hymenolepis diminuta (see MORENO & BARRETT, 1979) and Ascaris lumbricoides var. hominis (see MISHRA et al, 1978).…”

Section: Introductionmentioning

confidence: 99%

Monoamine oxidase in adult Ascaridia galli

1983

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Monoamine oxidase (MAO), catalysing oxidative deamination of biogenic monoamines, has been detected in adult Ascaridia galli. MAO was present in mitochondria and deaminated noradrenaline at the maximal rate, although serotonin, adrenaline, tyramine and dopamine were also degraded but more slowly. Of the organs studied, the body wall, female reproductive organ and intestine, the body wall (containing neuronal structures) showed highest MAO activity. Km value for chick ascarid mitochondrial MAO using tyramine as substrate was 1·66 x 10−3 M and it was most active at 2·5 mm tyramine concentration, pH 7·5 and 40°C. MAO of A. galli appeared to be thermolabile as nearly 80% of its activity was lost when the incubation temperature was increased 5° above optimum.

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Monoamine oxidase activity of shistosoma mansoni

Cited by 35 publications

References 39 publications

Classical transmitters and their receptors in flatworms

Classical transmitters and their receptors in flatworms

Structure-activity profiling of alkaloid natural product pharmacophores against a Schistosoma serotonin receptor

Monoamine oxidase in adult Ascaridia galli

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