monensin and lonomycin

The effects of sodium (monensin) and potassium (nigericin and lonomycin A) ionophores on the spontaneous activity in rabbit sino-atrial (SA) nodal cells were investigated using microelectrode and whole-cell voltage-clamp techniques. In the multicellular preparations, the ionophores produced a negative chronotropic effect in a concentration-dependent manner, and at 3x10(-5) M significantly decreased the amplitude and duration of action potentials and enhanced the maximum rate of depolarization. The ionophores elicited dysrhythmias and then a sinus arrest often occurred. These responses were reversible. In whole-cell clamp experiments, monensin enhanced the L-type Ca2+ current (ICa), whereas lonomycin A and nigericin inhibited ICa. The fast component of the inactivation phase for ICa was decreased by the ionophores, but the slow component was unaffected. The activation and inactivation kinetics (d infinity and f infinity) were not altered. The ionophores did not affect the hyperpolarization-activated inward current. Monensin inhibited the delayed rectifier K+ current (I(K)), but lonomycin A and nigericin increased I(K). Its activation kinetics shifted in the depolarizing direction. The effects on the ionic currents were irreversible. Monensin (30 microM) increased cellular Ca2+ concentration ([Ca2+]i), using Ca2+ -sensitive fluorescent dye (fura-2). These results indicate that the monovalent ionophores depress the action potentials and produce a negative chronotropic effect due to direct and indirect modulations of the ionic currents and the [Ca2+]i level in rabbit SA nodal cells.

Topics: Action Potentials; Animals; Calcium; Ionophores; Monensin; Nigericin; Rabbits; Sinoatrial Node; Time Factors

An in vitro study was carried out to evaluate the effect of different ionophore antibiotics and some of their derivatives on rumen fermentation and on the degradation of peanut meal nitrogen. The increase in the production of propionic acid at the expense of acetic acid, observed with lonomycin, nigericin, cationomycin and lysocellin, was identical to that noted with monensin. The decrease in methanogenesis observed in the presence of monensin was also found with cationomycin and lysocellin. With the exception of lysocellin, which greatly reduced protein degradation of peanut meal, and of nigericin, which had no effect on this parameter, the 2 other molecules presented the same action as monensin. The negative effect of monensin on microbial ammonia uptake was demonstrated with the same intensity in the presence of cationomycin; it was slightly higher with nigericin and particularly accentuated with lonomycin and lysocellin. Three ester derivatives of monensin (monensin acetate, monensin propionate and monensin butyrate) had a similar action to that of monensin on the orientation of rumen fermentations. The monensin isobutyrate derivative appeared to be more active than monensin and only weakly altered microbial ammonia uptake. The oxolonomycin and hydroxolonomycin derivatives behaved identically to lonomycin with respect to microbial metabolism and protein nitrogen degradation. Unlike the molecules from which they derive, the deacylated cationomycin and nigericic acid had no effect on the orientation of rumen fermentations. Of the compounds tested and presenting a potential 'growth-promoting action' at least comparable to that of monensin, and which demonstrated lower toxicity on mice, three molecules (oxolonomycin, lysocellin and cationomycin) appeared to present a zootechnical interest as feed additives for growing cattle.

Topics: Animals; Anti-Bacterial Agents; Ethers; Fermentation; Furans; Ionophores; Monensin; Nigericin; Nitrogen; Proteins; Rumen; Sheep

Lonomycin (TM-481, SQ 12,525) at various concentrations in the feed was tested in controlled battery experiments against laboratory strains of single and mixed Eimeria species infections. The experimental results indicated that lonomycin at doses of .003125, .00625, or .0125% demonstrated a high degree of anticoccidial activity by preventing or reducing mortality, reducing fecal dropping scores, and allowing for normal or near-normal weight gains against single and mixed infections of 5 major pathogenic species, E. acervulina, E. brunetti, E. maxima, E. necatrix, and E. tenella. Lonomycin, at these same dosages, was highly effective against a recent field isolate obtained from a flock previously fed monensin. These studies involving 7 trials totaling 1,680 broiler chicks, have demonstrated that lonomycin at levels of .003125 to .0125% (dependent on species of Eimeria) in the feed is an effective aid in the control of avian coccidiosis in broiler chickens.

Topics: Administration, Oral; Animal Feed; Animals; Anti-Bacterial Agents; Body Weight; Chickens; Coccidiosis; Coccidiostats; Ethers; Female; Lasalocid; Male; Monensin; Nigericin; Poultry Diseases