title: [The in vitro effect of alpha-2 agonists on thrombocyte function and density of thrombocyte alpha-2 receptors].
abstract: alpha 2-Agonists are being used increasingly in anaesthesia and intensive care medicine because of their antihypertensive, analgesic and sedative properties. Platelets bear alpha 2-receptors on the cell surface. Stimulation of these receptors by agonists induces platelet aggregation. The present study examined whether in vitro incubation of blood with the alpha 2-agonists clonidine and dexmedetomidine decreases alpha 2-receptor density and hereby influences platelet aggregation.
  
  
  METHODS
  Whole blood of 20 healthy volunteers was incubated over 24 h at 37 degrees C with 1 ng/ml clonidine or 1 or 10 ng/ml dexmedetomidine. Induced platelet aggregation was determined by means of turbidometry. Epinephrine (22 mumol/l) or collagen (20 mg/l) served as inductors. The density of alpha 2-receptors was measured in radioligand assays with 3H-Yohimbine. Phentolamine was used to assess unspecific binding. The data were analyzed with an analysis of variance.
  
  
  RESULTS
  Neither 1 ng/ml clonidine nor 1 ng/ml dexmedetomidine altered platelet aggregation or alpha 2-receptor density in comparison with the control sample. As a major result we found that 10 ng/ml dexmedetomidine caused a significant (P < 0.05) reduction in epinephrine-induced platelet aggregation (16.0 +/- 5.4%, n = 20, mean +/- SEM) compared with the control (46.0 +/- 1.3%, n = 20). alpha 2-Receptor density was not any different from the control.
  
  
  CONCLUSIONS
  This in vitro study showed that clinically relevant concentrations of 1 ng/ml clonidine or dexmedetomidine did not alter platelet aggregation or alpha 2-receptor density, even after 24 h exposure. However, 10 ng/ml dexmedetomidine was found to diminish significantly epinephrine-induced platelet aggregation, but did not change alpha 2-receptor density. This result showed that desensitization of platelet aggregation can occur without quantitative changes in alpha 2-receptors.
authors.affiliation: Abteilung Anaesthesiologie und Operative Intensivmedizin, Justus-Liebig-Universität Giessen.
authors.forename: M
authors.initials: M
authors.lastname: Heesen
authors.forename: G V
authors.initials: GV
authors.lastname: Dietrich
authors.forename: O
authors.initials: O
authors.lastname: Detsch
authors.forename: J
authors.initials: J
authors.lastname: Drevermann
authors.forename: J
authors.initials: J
authors.lastname: Boldt
authors.forename: G
authors.initials: G
authors.lastname: Hempelmann
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D020926:Medetomidine; D010646:Phentolamine; D010974:Platelet Aggregation / Q000187:drug effects; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015016:Yohimbine
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D003000:Clonidine; D020926:Medetomidine; D010646:Phentolamine