The role of histamine in platelet aggregation by physiological and immunological stimuli.
BACKGROUND
Platelets participate in allergic and inflammatory processes beside their role in haemostasis and thrombosis. This paper reports the level, the uptake, the metabolism and the release of histamine in human platelets. The effects of exogenous histamine, as well as the receptor and signal transduction of these effects, are also described.


METHODS
Purified suspensions of platelets, prepared from healthy volunteers and from atopic patients, were exposed in vitro to physiological and immunological stimuli. Platelet aggregation was measured by the increase in light transmission; histamine content and release, as well as cytosolic free Ca2+ concentration, were measured fluorimetrically. Platelet histamine forming capacity, and the uptake of exogenous histamine, were measured with a radioisotopic method.


RESULTS
Human platelets contain 72.5 +/- 9.6pmoles of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/- 3.5pmoles h(-1)g(-1) protein, which is reduced by alpha-fluoromethylhistidine (10(-5) M) a selective inhibitor of the specific histidine decarboxylase. Human platelets take up the preformed amine by a calcium and energy-dependent process, and the uptake of histamine is reduced by mepyramine, an H1-receptor antagonist, and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethanamine (10(-6) M), a blocker of intracellular histamine receptors. Histamine is also metabolized by human platelets. The exposure of platelets to thrombin (10-60 mUml(-1)) produced a progressive aggregation, associated with histamine release. The same is observed in platelets isolated from atopic patients exposed to anti-IgE antibodies. Exogenous histamine dose-dependently potentiates the aggregation induced by physiological and immunological stimuli. In resting platelets cytosolic calcium level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin as well as by anti-IgE; this effect is potentiated by 10(-5) M histamine.


CONCLUSIONS
The synergistic effect between histamine and other monoamines on platelet aggregation may explain some aspects of allergic vasculitis in which platelet aggregation is present.
Masini
E
E
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy. masini@server1.pharm.unifi.it
Di Bello
M G
MG
Raspanti
S
S
Ndisang
J F
JF
Fomusi Ndisang
J
J
Baronti
R
R
Cappugi
P
P
Mannaioni
P F
PF
D001792:Blood Platelets / Q000276:immunology* / Q000502:physiology*; D002118:Calcium / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000378:metabolism; D006636:Histamine Release; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D008762:Methylhistidines / Q000494:pharmacology; D010974:Platelet Aggregation; D011738:Pyrilamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000502:physiology; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D008762:Methylhistidines; D011969:Receptors, Histamine H1; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase; D011738:Pyrilamine; D002118:Calcium