Inhaled budesonide regimen enhances serotonin- and arachidonic acid-induced platelet aggregation.
The influence of inhaled budesonide regimen (400 micrograms x 2 for 7 days), on agonist-induced platelet aggregation and secretion, was investigated in 18 volunteers. Platelet activation induced by serotonin and arachidonic acid was significantly enhanced after budesonide, as demonstrated by an increase in aggregation velocity (Vmax) and amplitude (Amax), and in arachidonic acid-induced ATP-secretion. We found no change in platelet aggregation induced by ADP, epinephrine, and A23187. With the exception of epinephrine-induced platelet aggregation, which was inhibited by 10(-5)-10(-4) M budesonide, in vitro studies revealed no influence of 10 min budesonide preincubation (10(-9)-10(-4) M) on agonist-induced platelet activation, suggesting that the ex vivo enhancement of platelet function was mediated by secondary corticosteroid mechanisms. A tentative explanation of the increased arachidonic acid-induced platelet activation, may be a budesonide-induced stimulation of cyclooxygenase. The enhanced serotonin-induced platelet aggregation may be a reflection of exogenous corticosteroid stimulation of the 5-HT2-receptor.
Hasselmark
L
L
Department of Experimental Surgery, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Malmgren
R
R
Dumitrescu
A
A
D000255:Adenosine Triphosphate / Q000097:blood; D000280:Administration, Inhalation; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019819:Budesonide; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011282:Pregnenediones / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*
D001993:Bronchodilator Agents; D011282:Pregnenediones; D016718:Arachidonic Acid; D012701:Serotonin; D019819:Budesonide; D000255:Adenosine Triphosphate