A role for intracellular histamine in ultrastructural changes induced in platelets by phorbol esters

In human platelets, phorbol esters, such as phorbol-12-myristate-13-acetate (PMA), induce morphological changes, including pseudopod formation and the swelling and fusion of intracellular granule membranes with those of the surface-connected canalicular system, effects which have been attributed to activation of protein kinase C. However, a novel intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine. HCl (DPPE), previously has been shown to block PMA-induced aggregation independently of protein kinase C interaction, an effect reversible in permeabilized platelets by the addition of histamine. We now demonstrate that DPPE inhibits, in a concentration-dependent manner, the effects of PMA on human platelet ultrastructure. In permeabilized platelets, histamine reverses this inhibition, although it alone induces minimal effects on morphology. The results support a role for this amine to promote the labilization of platelet granules and pseudopod formation induced by PMA, presumably by acting in concert with additional PMA-activated pathways.