The Experts below are selected from a list of 588 Experts worldwide ranked by ideXlab platform

Biswanath Das - One of the best experts on this subject based on the ideXlab platform.

Digambar Balaji Shinde - One of the best experts on this subject based on the ideXlab platform.

Kip E. Panter - One of the best experts on this subject based on the ideXlab platform.

  • Running title: Optical isomers of Coniine inhibit fetal movement.
    2016
    Co-Authors: Benedict T Green, Kevin D Welch, James A Pfister, Stephen T. Lee, Kip E. Panter
    Abstract:

    Fetal-muscle type nicotinic acetylcholine receptor activation in TE-671 cells, and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid Coniine

  • Stereoselective Potencies and Relative Toxicities of γ-Coniceine and N-MethylConiine Enantiomers
    Chemical research in toxicology, 2013
    Co-Authors: Stephen T. Lee, Benedict T Green, Kevin D Welch, James A Pfister, Kip E. Panter, Glenn T. Jordan, Qian Zhang, David Hughes, Cheng-wei Tom Chang, Dale R. Gardner
    Abstract:

    γ-Coniceine, Coniine, and N-methylConiine are toxic alkaloids present in poison hemlock (Conium maculatum). We previously reported the comparison of the relative potencies of (+)- and (-)-Coniine e...

  • fetal muscle type nicotinic acetylcholine receptor activation in te 671 cells and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine alkaloid Coniine
    Journal of Pharmacology and Experimental Therapeutics, 2013
    Co-Authors: Benedict T Green, Kevin D Welch, James A Pfister, Kip E. Panter
    Abstract:

    Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock ( Conium maculatum L. ). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of Coniine actions at fetal muscle-type nAChR is lacking. The present study compared (−)-Coniine, (+)-Coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, α-conotoxins (CTx) EI and GI were used to antagonize the actions of (+)- and (−)-Coniine in TE-671 cells. (−)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (+)-Coniine, suggesting stereoselectivity by the receptor. The pyridine alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both Coniine enantiomers demonstrating concentration-dependent coagonism and selective antagonism. These results provide pharmacological evidence that the piperidine alkaloid Coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner.

  • Pregnant Goat Model by Optical Isomers of the Piperidine Alkaloid Coniine
    2012
    Co-Authors: Benedict T Green, Kevin D Welch, James A Pfister, Stephen T. Lee, Kip E. Panter
    Abstract:

    Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged de-sensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of Coniine actions at fetal muscle-type nAChR is lacking. The present study compared (2)-Coniine, (1)-Coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, a-conotoxins (CTx) EI and GI were used to antagonize the actions of (1)- and (2)-Coniine in TE-671 cells. (2)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (1)-Coniine, suggesting stereoselectivity by the receptor. The pyridine alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both Coniine enantiomers demon-strating concentration-dependent coagonism and selective an-tagonism. These results provide pharmacological evidence that the piperidine alkaloid Coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner

  • actions of piperidine alkaloid teratogens at fetal nicotinic acetylcholine receptors
    Neurotoxicology and Teratology, 2010
    Co-Authors: Benedict T Green, Kevin D Welch, Daniel Cook, Kip E. Panter, James A Pfister
    Abstract:

    Abstract Teratogenic alkaloids are found in many species of plants including Conium maculatum L., Nicotiana glauca, Nicotiana tabaccum, and multiple Lupinus spp. Fetal musculoskeletal defects produced by alkaloids from these plants include arthrogyropisis, scoliosis, torticollis, kyposis, lordosis, and cleft palate. A pharmacodynamic comparison of the alkaloids ammodendrine, anabasine, anabaseine, anagyrine, and Coniine in SH-SY5Y cells and TE-671 cells was made. These alkaloids and their enantiomers were more effective in depolarizing TE-671 cells which express the human fetal-muscle type nicotinic acetylcholine receptor (nAChR) relative to SH-SY5Y cells which predominately express autonomic nAChRs. The rank order of potency in TE-671 cells was: anabaseine > (+)-anabasine > (−)-anabasine > (±)-anabasine > anagyrine > (−)-Coniine > (±)-Coniine > (+)-Coniine > (±)-ammodendrine > (+)-ammodendrine. The rank order potency in SH-SY5Y cells was: anabaseine > (+)-anabasine > (−)-Coniine > (+)-Coniine > (+)-ammodendrine > anagyrine > (−)-anabasine > (±)-Coniine > (±)-anabasine > (−)-ammodendrine. The actions of these alkaloids at nAChRs in both cell lines could be distinguished by their maximum effects in depolarizing cell membrane potential. The teratogenic action of these compounds may be related to their ability to activate and subsequently desensitize nAChRs.

Gandham Satyalakshmi - One of the best experts on this subject based on the ideXlab platform.

Heiko Rischer - One of the best experts on this subject based on the ideXlab platform.

  • The killer of Socrates: Coniine and Related Alkaloids in the Plant Kingdom.
    Molecules (Basel Switzerland), 2017
    Co-Authors: Hannu Hotti, Heiko Rischer
    Abstract:

    Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine’s most famous victim is Socrates who was sentenced to death by poison chalice containing poison hemlock in 399 BC. In chemistry, Coniine holds two historical records: It is the first alkaloid the chemical structure of which was established (in 1881), and that was chemically synthesized (in 1886). In plants, Coniine and twelve closely related alkaloids are known from poison hemlock (Conium maculatum L.), and several Sarracenia and Aloe species. Recent work confirmed its biosynthetic polyketide origin. Biosynthesis commences by carbon backbone formation from butyryl-CoA and two malonyl-CoA building blocks catalyzed by polyketide synthase. A transamination reaction incorporates nitrogen from l-alanine and non-enzymatic cyclization leads to γ-coniceine, the first hemlock alkaloid in the pathway. Ultimately, reduction of γ-coniceine to Coniine is facilitated by NADPH-dependent γ-coniceine reductase. Although Coniine is notorious for its toxicity, there is no consensus on its ecological roles, especially in the carnivorous pitcher plants where it occurs. Lately there has been renewed interest in Coniine’s medical uses particularly for pain relief without an addictive side effect.

  • Metabolite profiling of the carnivorous pitcher plants Darlingtonia and Sarracenia
    PloS one, 2017
    Co-Authors: Hannu Hotti, Tuulikki Seppänen-laakso, Peddinti Gopalacharyulu, Heiko Rischer
    Abstract:

    Sarraceniaceae is a New World carnivorous plant family comprising three genera: Darlingtonia, Heliamphora, and Sarracenia. The plants occur in nutrient-poor environments and have developed insectivorous capability in order to supplement their nutrient uptake. Sarracenia flava contains the alkaloid Coniine, otherwise only found in Conium maculatum, in which its biosynthesis has been studied, and several Aloe species. Its ecological role and biosynthetic origin in S. flava is speculative. The aim of the current research was to investigate the occurrence of Coniine in Sarracenia and Darlingtonia and to identify common constituents of both genera, unique compounds for individual variants and floral scent chemicals. In this comprehensive metabolic profiling study, we looked for compound patterns that are associated with the taxonomy of Sarracenia species. In total, 57 different Sarracenia and D. californica accessions were used for metabolite content screening by gas chromatography-mass spectrometry. The resulting high-dimensional data were studied using a data mining approach. The two genera are characterized by a large number of metabolites and huge chemical diversity between different species. By applying feature selection for clustering and by integrating new biochemical data with existing phylogenetic data, we were able to demonstrate that the chemical composition of the species can be explained by their known classification. Although transcriptome analysis did not reveal a candidate gene for Coniine biosynthesis, the use of a sensitive selected ion monitoring method enabled the detection of Coniine in eight Sarracenia species, showing that it is more widespread in this genus than previously believed.

  • Mass spectrum of Coniine reference substance and detection of Coniine in the sample matrix.
    2017
    Co-Authors: Hannu Hotti, Tuulikki Seppänen-laakso, Peddinti Gopalacharyulu, Heiko Rischer
    Abstract:

    Mass spectrum of pure Coniine in SCAN mode (A) and selected fragments in SIM mode (B). Coniine detection in sample matrix (S. flava) in SCAN (C) and SIM modes (D).

  • Sarracenia accessions for targeted Coniine analysis by GC-MS (SIM).
    2017
    Co-Authors: Hannu Hotti, Tuulikki Seppänen-laakso, Peddinti Gopalacharyulu, Heiko Rischer
    Abstract:

    Sarracenia accessions for targeted Coniine analysis by GC-MS (SIM).

  • Polyketide synthases from poison hemlock (Conium maculatum L.)
    FEBS Journal, 2015
    Co-Authors: Hannu Hotti, Mikko Arvas, Teemu H. Teeri, Tuulikki Seppänen-laakso, Heiko Rischer
    Abstract:

    Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetyl-CoA and three malonyl-CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full-length enzymes by feeding different starter-CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl-CoA as a starter-CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of Coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl-CoA and two malonyl-CoAs. Database Nucleotide sequence data are available in GenBank/EMBL/DDBJ under the accession numbers KP726914, KP726915, KP726916, KP726917, KP726918, and KP726919