Inhibition of carbachol-induced inositol phosphate accumulation in the embryonic retina promoted by kainate and veratridine.
In the present study, we report that low concentrations of the glutamate ionotropic agonist kainate decreased the turnover of [3H]-phosphoinositides ([3H]-InsPs) induced by muscarinic receptors in the chick embryonic retina. When 100 microM carbachol was used, the estimated IC50 value for kainate was 0.2 microM and the maximal inhibition of approximately 50% was obtained with 1 microM or higher concentrations of the glutamatergic agonist. Our data also show that veratridine, a neurotoxin that increases the permeability of voltage-sensitive sodium channels, had no effect on [3H]-InsPs levels of the embryonic retina. However, 50 microM veratridine, but not 50 mM KCl, inhibited approximately 65% of the retinal response to carbachol. While carbachol increased [3H]-InsPs levels from 241.2 +/- 38.0 to 2044.5 +/- 299.9 cpm/mg protein, retinal response decreased to 861.6 +/- 113.9 cpm/mg protein when tissues were incubated with carbachol plus veratridine. These results suggest that the accumulation of phosphoinositides induced by activation of muscarinic receptors can be inhibited by the influx of Na+ ions triggered by activation of kainate receptors or opening of voltage-sensitive sodium channels in the chick embryonic retina.
Sanches
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Departamento de Neurobiologia, Universidade Federal Fluminense, Niterói, RJ, Brasil.
Ventura
A L
AL
D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors*; D002642:Chick Embryo; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000378:metabolism / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011189:Potassium Chloride; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D015222:Sodium Channels; D014701:Veratridine / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018721:Muscarinic Agonists; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D015222:Sodium Channels; D018698:Glutamic Acid; D011189:Potassium Chloride; D014701:Veratridine; D002217:Carbachol; D007608:Kainic Acid