Platelet-generated thromboxane A₂ enhances norepinephrine release from adrenergic nerves

Platelet-generated thromboxane A₂ enhances norepinephrine release from adrenergic nerves. Microsomes were prepared from outdated human platelets and incubated with arachidonic acid to produce thromboxane A₂. The incubate was added to isolated, electrically stimulated rabbit portal veins to determine its effect on adrenergic neurotransmission. Immunoreactive thromboxane B₂ concentrations were measured to assess the generation of the precursor, thromboxane A₂. Addition of microsomes in the presence of arachidonic acid (1 μM) caused a concentration-dependent increase in thromboxane B₂ concentrations, electrically induced force and norepinephrine release. Inclusion of acetylsalicylic acid (10 μM) or the thromboxane synthase inhibitor, U63557A (100 μg/ml), in the arachidonic acid-microsome incubate eliminated the potentiation of force, norepinephrine release and thromboxane B₂ generation. The thromboxane receptor antagonist, SQ30741 (1 μM), also eliminated the microsome effects on neurogenic force and norepinephrine release but not on thromboxane generation. The microsome-arachidonic acid incubate did not influence norepinephrine concentration-contractile response curves. These data are consistent with a potentiative action of thromboxane A₂ on adrenergic neurotransmission, primarily mediated by enhanced release of norepinephrine. The physiological or pathological significance of this observation depends on the thromboxane concentrations in the vicinity of adrenergic nerves.