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

Abimael D Rodriguez - One of the best experts on this subject based on the ideXlab platform.

Elias A Couladouros - One of the best experts on this subject based on the ideXlab platform.

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

  • 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, K 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.

  • actions of Piperidine Alkaloid teratogens at fetal nicotinic acetylcholine receptors
    Neurotoxicology and Teratology, 2010
    Co-Authors: Benedict T Green, K E Panter, Kevin D Welch, Daniel Cook, 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.

  • quinolizidine and Piperidine Alkaloid teratogens from poisonous plants and their mechanism of action in animals
    Veterinary Clinics of North America-food Animal Practice, 1993
    Co-Authors: K E Panter, Richard F Keeler
    Abstract:

    Quinolizidine and Piperidine Alkaloid teratogens from Lupinus,Conium, and Nicotiana genera have been identified as causes ofbirth defects in livestock induced by poisonous plants. Manydefects now known to be related to poisonous plant ingestionwere once thought to have a genetic origin. This suppositiondelayed diagnosis, reporting, and understanding of such birthdefects, because breeders and producers feared the news wouldmake it difficult to sell breeding stock. Defects caused by quinolizidineand Piperidine teratogens include cleft palate andcontracture-type skeletal defects such as arthrogryposis, scoliosis,torticollis, and kyphosis. Teratogens have been identified,differences in susceptibility to teratogenic compounds amonglivestock species have been elucidated, periods of gestation whenspecific types of birth defects occur have been determined, andinformation about mechanism of action has been developed.

  • multiple congenital contractures mcc and cleft palate induced in goats by ingestion reduction in fetal movement as the probable cause of Piperidine Alkaloid containing plants
    1990
    Co-Authors: K E Panter, R F Keeler, T D Bunch, D V Sisson, R J Callan
    Abstract:

    Fetal movement, observed by ultrasound imaging, was significantly reduced (P 5 0.001) in pregnant goats gavaged with Conium seed and Nicofiunu gZaucu and temporarily reduced with fresh Conium plant. Conium seed and Nicofiunu gZuucu induced cleft palate and multiple congenital contractures in 100% of the kids born to pregnant goats gavaged with these plants. Multiple congenital contractures included torticollis, scoliosis, lordosis, arthrogryposis, rib cage anomalies, over extension, and flexure and rigidity of the joints. However, in goats gavaged with fresh Conium plant, fetal movement was inhibited for only about 5 hours after each individual dosage and gradually returned to control levels 12 hours after dosing. Fetal malformations in this group were limited from modest to moderate contractures of the front limbs, which resolved by 8-10 weeks post partum. No cleft palates were induced. Fetal movement was not inhibited in goats fed Lupinus cuudutus and no cleft palates or multiple congenital contractures were induced in their offspring. The duration of the reduction in fetal movement appears to be an important factor in the severity and permanence of the deformities, particularly with cleft palate, spinal column defects, and severe joint deviation and fixation.

Kunio Ogasawara - One of the best experts on this subject based on the ideXlab platform.