RH-3421, a potent dihydropyrazole insecticide, inhibits depolarization-stimulated rises in free [Ca2+] and 45Ca2+ uptake in mammalian synaptosomes.
The dihydropyrazole RH-3421 inhibits veratridine- and K(+)-induced rises in synaptosomal free Ca2+ with IC50s of 0.2 and 1 microM, respectively. The K(+)-induced rise in free synaptosomal Ca2+, which requires external Ca2+, is also blocked by RH-3421 in the presence of tetrodotoxin. The K(+)-stimulated 45Ca2+ uptake by synaptosomes is unaffected by tetrodotoxin, blocked by cobalt ions and inhibited by RH-3421 both alone (IC50 = 11 microM) and in the presence of tetrodotoxin. RH-3421 does not influence the level of free Ca2+ or basal 45Ca2+ uptake in non-depolarized synaptosomes. The results suggest RH-3421 inhibits voltage-sensitive calcium channels in nerve endings.
Zhang
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Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada.
Nicholson
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002127:Calcium Isotopes; D007306:Insecticides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D002127:Calcium Isotopes; D007306:Insecticides; D010671:Phenylurea Compounds; D011720:Pyrazoles; D015222:Sodium Channels; D013779:Tetrodotoxin; D014701:Veratridine; C072441:RH 3421; D002118:Calcium