The actions of ivermectin on cultured chick spinal cord neurons

doi:10.1016/0304-3940(86)90494-5

Neuroscience Letters

Volume 69, Issue 3, 12 September 1986, Pages 279-284

https://doi.org/10.1016/0304-3940(86)90494-5 Get rights and content

Abstract

The effects of ivermectin (IVM) on cultured chick spinal neurons sensitive to GABA agonists were investigated. IVM caused a change of membrane potential which was associated with an increase in membrane conductance, apparently reversed at about −40 mV and weakened by repetitive application. Furthermore, this agent did not have any effects on either the actions of GABA agonists on neurons or [³H]GABA efflux from those cells. These results suggest that IVM increases membrane conductance through sites which are different from GABA recognition sites.

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Cited by (8)

Activation of rat recombinant α<inf>1</inf>β<inf>2</inf>γ(2S) GABA(A) receptor by the insecticide ivermectin
2000, European Journal of Pharmacology
In the present study, the activation of rat recombinant α₁β₂γ_2S γ-aminobutyric acid (GABA)-ergic Cl⁻ channel expressed in human embryonic kidney (HEK) 293 cells by ivermectin was investigated. Maximal activation of the channel occurred with GABA concentrations of 10 mM or 20 μM ivermectin both achieving about the same current amplitudes. With those saturating concentrations, the currents rose with GABA within 1 ms to the maximal values, whereas the rise time for ivermectin was about 500 times longer. In contrast to activation with GABA, no desensitisation in the presence of the agonist was observed with ivermectin. With both agonists, two different open states were detected. On simultaneous application of GABA and ivermectin the current amplitudes and the kinetics were determined by the agonist applied in the concentration eliciting the higher open probability. It is concluded that GABA and ivermectin activated the channel independently resulting in different kinetic properties.
Avermectin binding in Caenorhabditis elegans. A two-state model for the avermectin binding site
1989, Biochemical Pharmacology
Specific binding sites for ivermectin (IVM; 22,23-dihydroavermectin-B₁) were identified and characterized in a crude membrane fraction prepared from the nematode, Caenorhabditis elegans (C. elegans). Specific [³H]IVM binding was saturable with an apparent dissociation constant, K_d, of 0.26 nM and a receptor concentration of 3.53 pmol/mg protein. [³H]IVM binding in C. elegans was linear with tissue protein concentration, and optimal binding occurred within a pH range of 7.3 to 7.6. Kinetic analysis of the binding showed that the reaction proceeded by a two-step mechanism. Initially, a rapidly reversible complex was formed and, after additional incubation, this complex was transformed to a much more slowly reversible complex. Stereospecificity of [³H]IVM binding to C. elegans membranes was demonstrated by competition with a series of avermectin derivatives. The in vivo effects of IVM and its derivatives on C. elegans motility were concentration dependent and correlated well with their relative binding affinities. Several putative neurotransmitters including γ-aminobutyric acid (GABA), carbamyl choline, taurine, glutamate and dopamine were tested and found to have no effect on IVM binding. Specific IVM binding sites were also identified in rat brain; however, the affinity was approximately 100-fold lower than that observed in C. elegans and Stereospecificity studies demonstrated structural differences in the two binding sites. These results are the first direct demonstration of a specific IVM binding site in nematodes and thus are important in furthering our understanding of its mode of action.
Macrolide compounds, ivermectin and milbemycin D, stimulate chloride channels sensitive to gabaergic drugs in cultured chick spinal neurons
1989, Comparative Biochemistry and Physiology. Part C, Comparative
- 1.
  1. The effects of ivermectin (IVM) and milbemycin D (MMD) on cultured embryonic spinal neurons were investigated, using the whole-cell recording technique.
- 2.
  2. IVM and MMD caused Cl⁻ current under voltage-clamp conditions.
- 3.
  3. The reversal potential of the MMD-evoked Cl⁻ current was shifted in a positive direction when half of the external Cl⁻ was substituted by isethionate.
- 4.
  4. The MMD-evoked current was inhibited by picrotoxinin and bicuculline, whereas it was enhanced by diazepam.
- 5.
  5. Different characteristics of desensitization were observed between the MMD- (IVM-) and muscimol-induced effects.
- 6.
  6. These results suggest that IVM and MMD directly activate the Cl⁻ channel through their specific sites modulated by GABAergic drugs.
Actions of avermectins on cultured neurons
1988, General Pharmacology
Avermectin B(1a) binds to high- and low-affinity sites with dual effects on the γ-aminobutyric acid-gated chloride channel of cultured cerebellar granule neurons
1997, Journal of Pharmacology and Experimental Therapeutics
Activation of Cl<sup>-</sup> channels by avermectin in rat cultured hippocampal neurons
1993, Naunyn-Schmiedeberg's Archives of Pharmacology

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The actions of ivermectin on cultured chick spinal cord neurons

Abstract

Brain Res.

J. Neurosci. Meth.

Eur. J. Pharmacol.

Brain Res.

Neuropharmacology

Biochem. Biophys. Res. Commun.

Eur. J. Pharmacol.

GABA conductance of chick spinal cord and dorsal root ganglion neurons in cell culture

J. Neurophysiol.