Interactions between alpha-latrotoxin and trivalent cations in rat striatal synaptosomal preparations.
The interactions between alpha-latrotoxin (alpha-LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al3+, Y3+, La3+, Gd3+, and Yb3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of alpha-LTx-induced [3H]dopamine [( 3H]DA) release (order of potency: Yb3+ greater than Gd3+ approximately Y3+ greater than La3+ greater than Al3+). Only with Al3+ could inhibition of [3H]DA release be attributed to a block of 125I-alpha-LTx specific binding to synaptosomal preparations. The inhibitory effect of trivalent ions was reversible provided synaptosomes were washed with buffer containing EDTA. Trivalent ions also inhibited alpha-LTx-induced [3H]DA release at times when alpha-LTx-stimulated release was already evident. alpha-LTx-induced synaptosomal membrane depolarization was blocked by La3+, but not affected by Gd3+, Y3+, and Yb3+. alpha-LTx-stimulated uptake of 45Ca2+ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit alpha-LTx action in rat striatal synaptosomal preparations: (1) inhibition of alpha-LTx binding (Al3+); (2) inhibition of alpha-LTx-induced depolarization (La3+); and (3) inhibition of alpha-LTx-induced 45Ca2+ uptake (Gd3+, Y3+, Yb3+, La3+).
Scheer
H W
HW
Department of Pharmacology, Université de Montréal, Quebec, Canada.
D000535:Aluminum / Q000494:pharmacology; D000818:Animals; D001180:Arthropod Venoms / Q000494:pharmacology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D002412:Cations / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D005682:Gadolinium / Q000494:pharmacology; D007202:Indicators and Reagents; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009861:Onium Compounds / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013111:Spider Venoms / Q000378:metabolism / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014320:Triphenylmethyl Compounds / Q000378:metabolism; D015018:Ytterbium / Q000494:pharmacology; D015019:Yttrium / Q000494:pharmacology
D001180:Arthropod Venoms; D002132:Calcium Radioisotopes; D002412:Cations; D007202:Indicators and Reagents; D009861:Onium Compounds; D013111:Spider Venoms; D014320:Triphenylmethyl Compounds; C011561:triphenylmethylphosphonium; D015019:Yttrium; C020763:alpha-latrotoxin; D007811:Lanthanum; D005682:Gadolinium; D000535:Aluminum; D015018:Ytterbium; D004298:Dopamine