POLYAMINES ALLOSTERICALLY MODULATE [H-3] 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. [H-3]Diltiazem binding was inhibited by arcaine (IC50 = 55-mu-M) and, in decreasing order of potency, by agmatine, spermidine, spermine and putrescine. Under control conditions, only spermidine and spermine allosterically inhibited [H-3]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 [H-3]nitrendipinc, in a manner analogous to that shown previously for Ca2+. Thus, polyamines may function as endogenous modulators of the voltage-dependent Ca2+ channel.