TY - JOUR
T1 - Platelet-generated thromboxane A2 enhances norepinephrine release from adrenergic nerves
AU - Trachte, George J
AU - Stein, E.
PY - 1988
Y1 - 1988
N2 - 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 Microsomes were prepared from outdated human platelets and incubated with arachidonic acid to produce thromboxane A2.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.
AB - 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 Microsomes were prepared from outdated human platelets and incubated with arachidonic acid to produce thromboxane A2.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.
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M3 - Article
C2 - 2849661
AN - SCOPUS:0024234685
SN - 0022-3565
VL - 247
SP - 1139
EP - 1145
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -