Study on the cupric phenanthroline-induced serotonin release in digitonin-permeabilized platelets.

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Abstract
Digitonin-permeabilized rabbit platelets released serotonin dose-dependently in response to cupric phenanthroline, which is a mild oxidant which catalyzes the formation of disulfide bridges. The serotonin release induced by cupric phenanthroline was inhibited by ethylene glycol bis(.beta.-aminoethylether)N,Nd''-tetraacetic acid (EGTA), but EGTA did not restore the decrease in protein-bound free sulfhydryls of permeable platelets. An alternation in calcium movements was suggested to be implicated in the serotonin release from cupric phenanthroline-treated permeable platelets. The agent suppressed the calcium uptake to calcium-storage sites, probably the dense tubular system, and enhanced the calcium efflux. Moreover, it tended to inhibit Ca2+-adenosene triphosphatase of permeable platelets. On the other hand, a sulfhydryl modifier, chloromercuriphenylsulfonic acid, also decreased the amount of free sulfhydryls in protein and released serotonin in permeable platelets, but EGTA did not inhibit ether reaction. Neither cupric phenanthroline nor chloromercuriphenylsulfonic acid elicited serotonin release from intact platelets. It is suggested that both agents act on intra-platelet target molecules to exert their effects, but the mechanisms involved are different.