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.
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
A
A
McNicol
S P
SP
Saxena
L J
LJ
Brandes
J M
JM
Gerrard
D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008854:Microscopy, Electron; D010647:Phenyl Ethers / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D010647:Phenyl Ethers; D006632:Histamine; C043062:tesmilifene; D013755:Tetradecanoylphorbol Acetate