Aspirin, prostaglandin E1 and Quin-2 AM-induced platelet dysfunction: restoration of function by noradrenalin.
Studies from our laboratory have demonstrated that adrenalin can restore the function of drug-induced refractory platelets to the action of physiological agonists via a novel mechanism (membrane modulation). In various disease states and clinical conditions the circulating levels of noradrenalin (NA) increase several fold more than adrenalin. Therefore, in this study the influence of NA on three well characterized platelet refractory models has been evaluated. Aspirin-exposed platelets were obtained for these studies from blood of donors who had taken one baby aspirin (80 mgs) per day for four consecutive days. Prostaglandin-exposed platelets were obtained by disaggregating ADP-induced aggregates through addition of prostaglandin E1 (1 microM). Finally, low calcium platelets were obtained by buffering cytosolic free calcium with a calcium specific cell permeant fluorophore, Quin-2 AM (60 microM). Drug-exposed platelets did not aggregate irreversibly when stirred with arachidonate (0.45 mM) or NA 5 microM). However, when treated with NA first, drug-treated platelets regained their sensitivity to the action of arachidonate and aggregated irreversibly. The ability of NA to restore the sensitivity of drug-induced refractory platelets was effectively blocked by yohimbine (10 microM), an alpha 2 adrenoceptor antagonist. Results of these studies suggest that NA, similar to the action of adrenalin, can activate membrane modulation and restore the sensitivity of platelets to the action of physiological agonists under a variety of experimental conditions.
Rao
G H
GH
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
White
J G
JG
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000634:Aminoquinolines; D001095:Arachidonic Acids; D010975:Platelet Aggregation Inhibitors; D011942:Receptors, Adrenergic, alpha; D016718:Arachidonic Acid; D015016:Yohimbine; D000527:Alprostadil; C035739:Quin2; D001241:Aspirin; D002118:Calcium; D009638:Norepinephrine