Decreased alpha-adrenergic receptors in newborn platelets: cause of abnormal response to epinephrine.
Platelets of newborn infants fail to aggregate or release adenosine diphosphate in response to epinephrine. Because epinephrine-induced aggregation is an alpha-adrenergic event, we considered the possibility that newborn platelets possess fewer alpha-adrenergic receptors than do those of adults. Therefore we compared the specific binding of the alpha-adrenergic antagonist, [3H]-dihydroergocryptine (DHE), in intact washed platelets prepared from paired samples of maternal and cord platelet-rich plasma. Newborn platelets demonstrated normal kinetics of [3H]-DHE binding and normal affinity for [3H]-DHE. Scatchard analysis of [3H]-DHE binding indicated a single class of binding sites that exhibited a high affinity for the radioligand (Kd = 10 nM). Maternal platelets were found to bind approximately 2-fold more [3H]-DHE than newborn platelets (3.70 +/- 0.28 vs. 1.74 +/- 0.17 fmol/10(7) platelets) at saturation. This corresponds to 223 +/- 17 vs. 105 +/- 11 binding sites per platelet (p less than 0.001). Repeat washing of newborn platelets did not yield increased [3H]-DHE binding suggesting the binding sites had not previously been masked by elevated circulating levels of catecholamines in venous cord blood. When control platelets were incubated with concentrations of [3H]-DHE that half-saturated the alpha-adrenergic receptors, diminution of platelet function comparable to that seen in newborn platelets was observed. Since maternal and newborn platelets are similar size, it appears that a deficiency of alpha-adrenergic receptors may account for the diminished response of newborn platelets to epinephrine.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D004088:Dihydroergotoxine; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D000244:Adenosine Diphosphate; D009638:Norepinephrine; D004837:Epinephrine