Metabolism of biogenic monoamines in the ciliated protozoan, Tetrahymena pyriformis

Takeda, Norihiko; Sugiyama, Kanji

doi:10.1016/0742-8413(93)90255-j

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…Although they are considered to be inactive metabolites in higher organisms, epinine and metanephrine are biologically active in some protozoa and invertebrates. For instance, epinine replaces noradrenaline as the major substrate for adrenaline biosynthesis in the unicellular protozoan Tetrahymena pyriformi [48]. In the cnidarian, sea pansy Renilla koellikeri , epinine, metanephrine and another related metabolite, normetanephrine, are all present at high levels and are believed to be neuroactive [49].…”

Section: Discussionmentioning

confidence: 99%

A Novel G Protein-Coupled Receptor of Schistosoma mansoni (SmGPR-3) Is Activated by Dopamine and Is Widely Expressed in the Nervous System

El-Shehabi¹,

Taman²,

Moali³

et al. 2012

PLoS Negl Trop Dis

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Schistosomes have a well developed nervous system that coordinates virtually every activity of the parasite and therefore is considered to be a promising target for chemotherapeutic intervention. Neurotransmitter receptors, in particular those involved in neuromuscular control, are proven drug targets in other helminths but very few of these receptors have been identified in schistosomes and little is known about their roles in the biology of the worm. Here we describe a novel Schistosoma mansoni G protein-coupled receptor (named SmGPR-3) that was cloned, expressed heterologously and shown to be activated by dopamine, a well established neurotransmitter of the schistosome nervous system. SmGPR-3 belongs to a new clade of “orphan” amine-like receptors that exist in schistosomes but not the mammalian host. Further analysis of the recombinant protein showed that SmGPR-3 can also be activated by other catecholamines, including the dopamine metabolite, epinine, and it has an unusual antagonist profile when compared to mammalian receptors. Confocal immunofluorescence experiments using a specific peptide antibody showed that SmGPR-3 is abundantly expressed in the nervous system of schistosomes, particularly in the main nerve cords and the peripheral innervation of the body wall muscles. In addition, we show that dopamine, epinine and other dopaminergic agents have strong effects on the motility of larval schistosomes in culture. Together, the results suggest that SmGPR-3 is an important neuronal receptor and is probably involved in the control of motor activity in schistosomes. We have conducted a first analysis of the structure of SmGPR-3 by means of homology modeling and virtual ligand-docking simulations. This investigation has identified potentially important differences between SmGPR-3 and host dopamine receptors that could be exploited to develop new, parasite-selective anti-schistosomal drugs.

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Section: Discussionmentioning

confidence: 99%

A Novel G Protein-Coupled Receptor of Schistosoma mansoni (SmGPR-3) Is Activated by Dopamine and Is Widely Expressed in the Nervous System

El-Shehabi¹,

Taman²,

Moali³

et al. 2012

PLoS Negl Trop Dis

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“…In vertebrates and multicultural organisms, hormones and neurotransmitters act as messengers that control and co-operate the activities of specialized cells. Vertebratelike hormones, neurotransmitter and biogenic monoamines have been detected in the unicellular protozoan, Tetrahymena pyriformis (Brizzi and Blum, 1970;Goldman et al, 1981;Gundersen and Thompson, 1983;Le Roith and Roth, 1985;Naokuni and Kanji, 1993). These authors investigated and detected biogenic monoamines from a variety of biological samples with the use of HPLC-EcD rather than exogenous catecholamine pressure in Tetrahymena.…”

Section: Introductionmentioning

confidence: 99%

ISTA13‐catecholamine toxicity and metabolism in the ciliated protozoan, Tetrahymena pyriformis

Ud-Daula

Pfister

Schramm

2008

Environmental Toxicology

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A high throughput culture methodology of unicellular eukaryote Tetrahymena pyriformis, strain GL were used for the determination of catecholamines toxicity and their metabolism. Catecholamines exhibited acute toxicity to Tetrahymena cells where dopamine and L-DOPA showed higher toxic potential of EC(10) (0.39 and 0.63 mg/L, respectively) and EC(20) (1.1 and 1.0 mg/L, respectively). All the testing catecholamines were highly degradable in the PPY-medium due to the oxidizing environment during incubation. They were also naturally synthesized and released by Tetrahymena cells into the culture medium and increasingly accumulated with time where as noradrenalin demonstrated significant results. Cells were exposed with physiological concentration (0.12 mg/L) and one higher concentration (8.0 mg/L) of catecholamines, resulting noradrenalin depletion and in vivo generation of a metabolite in response to dopamine with higher concentration treatment. This dopamine metabolite was relatively nonpolar compared with the catecholamines and was eluted later from the reverse phase C-18 column.

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Serotonin-degradative pathways in the toad (Bufo bufo japonicus) brain: clues to the pharmacological analysis of human psychiatric disorders

Takeda

1994

Comparative Biochemistry and Physiology Part C: Pharmacology, T

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Metabolism of biogenic monoamines in the ciliated protozoan, Tetrahymena pyriformis

Cited by 5 publications

References 19 publications

A Novel G Protein-Coupled Receptor of Schistosoma mansoni (SmGPR-3) Is Activated by Dopamine and Is Widely Expressed in the Nervous System

A Novel G Protein-Coupled Receptor of Schistosoma mansoni (SmGPR-3) Is Activated by Dopamine and Is Widely Expressed in the Nervous System

ISTA13‐catecholamine toxicity and metabolism in the ciliated protozoan, Tetrahymena pyriformis

Serotonin-degradative pathways in the toad (Bufo bufo japonicus) brain: clues to the pharmacological analysis of human psychiatric disorders

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