Activation of single nicotinic receptor channels from Caenorhabditis elegans muscle. (1/8)

Nicotinic acetylcholine receptors (nAChRs) are pentameric neurotransmitter-gated ion channels that mediate synaptic transmission throughout the nervous system in vertebrates and invertebrates. Caenorhabditis elegans is a nonmammalian model for the study of the nervous system and a model of parasitic nematodes. Nematode muscle nAChRs are of considerable interest because they are targets for anthelmintic drugs. We show single-channel activity of C. elegans muscle nAChRs for the first time. Our results reveal that in the L1 larval stage acetylcholine (ACh) activates mainly a levamisole-sensitive nAChR (L-AChR). A single population of 39 pS channels, which are 5-fold more sensitive to levamisole than ACh, is detected. In contrast to mammalian nAChRs, open durations are longer for levamisole than for ACh. Studies in mutant strains reveal that UNC-38, UNC-63, and UNC-29 subunits are assembled into a single L-AChR in the L1 stage and that these subunits are irreplaceable, suggesting that they are vital for receptor function throughout development. Recordings from a strain mutated in the LEV-1 subunit show a main population of channels with lower conductance (26 pS), prolonged open durations, and reduced sensitivity to levamisole. Thus, although LEV-1 is preferentially incorporated into native L-AChRs, receptors lacking this subunit can still function. No single-channel activity from levamisole-insensitive nAChRs is detected. Thus, during neuromuscular transmission in C. elegans, the majority of ACh-activated current flows through L-AChRs. This study contributes to the understanding of the molecular mechanisms underlying functional diversity of the nAChR family and offers an excellent strategy to test novel antiparasitic drugs.  (+info)

Morantel allosterically enhances channel gating of neuronal nicotinic acetylcholine alpha 3 beta 2 receptors. (2/8)

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Glutamine 57 at the complementary binding site face is a key determinant of morantel selectivity for {alpha}7 nicotinic receptors. (3/8)

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The positive allosteric modulator morantel binds at noncanonical subunit interfaces of neuronal nicotinic acetylcholine receptors. (4/8)

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Specificity determinants of allosteric modulation in the neuronal nicotinic acetylcholine receptor: a fine line between inhibition and potentiation. (5/8)

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Effect of an anthelmintic program with morantel tartrate on the performance of beef cattle. (6/8)

A field trial was conducted to determine (1) the effectiveness of an anthelmintic program using morantel tartrate (MT) to control subclinical gastrointestinal parasitism among cattle on pasture and (2) the effects of the program on the performance of cattle. Two Hereford herds, each on a separate pasture with forage of comparable quality and quantity, were used. A stocking rate of .62 ha/cow-calf was maintained in both pastures. One herd consisted of 124 cows and 122 calves and served as a non-mediated control group. The second herd consisted of 126 cows and 124 calves. Cows and calves from the latter group were treated with a bolus formulation of MT at a dosage of 10 mg/kg body weight at the beginning of the trial and again 55 d later. Calves were treated again 42 d after the second treatment. Cattle were weighed individually each month and rectal fecal samples for nematode egg counts were obtained from 36 cows and 36 calves from each group at that time. These donor cattle were selected at random at the time of the first weighing; fecal samples were then obtained from the same animals throughout the study. Eggs of the Cooperia-Ostertagia-Trichostrongylus complex predominated in all fecal samplings. There was no difference in the number of nematode eggs from the two groups of cows. However, the medicated cows gained significantly more weight than the controls and had an average weight gain advantage of 28.8 kg. The medicated calves had significantly lower average egg counts and made higher weight gains than the unmedicated calves. The medicated calves had an average weight gain advantage over the control group of 11.1 kg.  (+info)

Milk production effect of a morantel tartrate treatment at calving in dairy cows with subclinical parasitism. (7/8)

A field trial involving 217 dairy cows from 13 herds located in four different areas of Quebec was conducted to determine the level of subclinical parasitism. The effect on milk production was evaluated on 116 cows following a single anthelmintic treatment with morantel tartrate administered at freshening. The results showed that this treatment increased milk production in nine herds, which was statistically significant at P 0.05).  (+info)

Activation and cooperative multi-ion block of single nicotinic-acetylcholine channel currents of Ascaris muscle by the tetrahydropyrimidine anthelmintic, morantel. (8/8)

1. We have investigated activation and block, by the tetrahydropyrimidine anthelmintic, morantel, of nicotinic-acetylcholine receptor (AChR) currents in membrane vesicles isolated from somatic muscle cells of the nematode parasite Ascaris suum. Standard single-channel recording techniques were employed. Morantel in the pipette (6 nM to 600 microM), activated single nicotinic AChR currents. 2. Kinetic properties of the main-conductance state of morantel-activated currents were investigated in detail throughout the concentration range, 0.6 microM to 600 microM. Open-time distributions were best fitted by a single exponential. Mean open-times were slightly voltage-dependent, increasing from 0.9 ms at +75 mV to 1.74 ms at -75 mV in the presence of 0.6 microM morantel. At low concentrations, closed-time distributions were best fitted by the sum of two or three exponential components. 3. As the concentration of morantel was increased (100-600 microM), fast-flickering open channel-block was observed at positive potentials, even though morantel, a cation, was only present at the extracellular surface of the membrane. The block rate was dependent on morantel concentration and both block rate and duration of block increased as the potential became less positive. A simple channel-block mechanism did not explain properties of this block. 4. At negative potentials, as the morantel concentration increased, a complex block was observed. With increases in morantel concentration two additional gap components appeared in closed-time distributions: one was short with a duration (approximately 13 ms) independent of morantel concentration; the other was long with a duration that increased with morantel concentration (up to many minutes). In combination, these two components produced a marked reduction in probability of channel opening (Po) with increasing morantel concentration. The relationship between the degrees of block and morantel concentration had a Hill coefficient of 1.6, suggesting the involvement of at least two blocking molecules. The data were analysed by use of a simple sequential double block kinetic model.  (+info)