Histamine formed in stimulated human platelets is cytoplasmic.

The localization of histamine formed by human platelets in response to agonists was evaluated. 87 +/- 5% of the histamine in a suspension of platelets exposed to phorbol-12-myristate-13-acetate (PMA) was associated with the platelet pellet. Incubation of saponin-permeabilized platelets with the intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), released 75 +/- 3.9% of the histamine into the supernatant. Under conditions where 90% of platelet serotonin was secreted into the supernatant, the majority (80%) of platelet histamine remained associated with the pellet. The results suggest that histamine synthesized in response to agonists is largely cytoplasmic.