Polyamines allosterically modulate [3H]nitrendipine binding to the voltage-sensitive calcium channel in rat brain.
The effects of polyamines on radioligand binding to the slow voltage-dependent Ca2+ channel were studied using membranes from the rat cerebral cortex. [3H]Diltiazem binding was inhibited by arcaine (IC50 = 55 microM) and, in decreasing order of potency, by agmatine, spermidine, spermine and putrescine. Under control conditions, only spermidine and spermine allosterically inhibited [3H]nitrendipine binding while arcaine, agmatine and putrescine were inactive. Nevertheless, putrescine antagonized the effect of spermine as well as the allosteric effects of diltiazem and verapamil on the binding of [3H]nitrendipine, in a manner analogous to that shown previously for Ca2+. Thus, polyamines may function as endogenous modulators of the voltage-dependent Ca2+ channel.
Schoemaker
H
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Department of Biology, Synthelabo Recherche (L.E.R.S.), Bagneux, France.
D000494:Allosteric Regulation; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism*; D004110:Diltiazem / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009568:Nitrendipine / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D015220:Calcium Channels; D011073:Polyamines; D014316:Tritium; D009568:Nitrendipine; D004110:Diltiazem