title: Bidirectional effects of dexmedetomidine on human platelet functions in vitro.
abstract: Platelets express the imidazoline (I)-receptor, I1 and I2, as well as the α2-adrenoceptor. Although dexmedetomidine, a selective α2-adrenoceptor agonist with some affinity for the I-receptor is expected to affect platelet function, the effects of dexmedetomidine on platelet functions remain unclear. In the present study, we investigated the effects of dexmedetomidine on human platelet functions in vitro. The effects of dexmedetomidine on platelet aggregation were examined using aggregometers. The formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in platelets was measured by an enzyme immunoassay. In addition, P-selectin expression in platelets was estimated by flow cytometry. We showed that dexmedetomidine enhances platelet aggregation. But in the presence of yohimbine, an α2-antagonist, dexmedetomidine suppressed platelet aggregation. Efaroxan, an I1-antagonist, and methylene blue, a soluble guanylate cyclase inhibitor, abolished the suppressive effect of dexmedetomidine, whereas idazoxan, an I2-antagonist, showed no effect. Dexmedetomidine suppressed cAMP formation and enhanced P-selectin expression in platelets, and these effects were inhibited by yohimbine. Dexmedetomidine increased cGMP formation in platelets in the presence of yohimbine, and this increase was suppressed by efaroxan. These results demonstrated that dexmedetomidine has both enhancing and suppressive effects on human platelet functions through its action on the α2-adrenoceptor and on the I1-imidazoline receptor, respectively.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: shuji-kawamoto@ares.eonet.ne.jp.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kawamoto
authors.affiliation: Department of Anesthesia, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa mukaihata-cho, Fushimi-ku, Kyoto 612-8555, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Hirakata
authors.affiliation: Department of Psychiatry, Kyoto University Hospital, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sugita
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D006801:Humans; D054755:Imidazoline Receptors / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D054755:Imidazoline Receptors; D019007:P-Selectin; C410887:imidazoline I1 receptors; D020927:Dexmedetomidine; D000242:Cyclic AMP; D006152:Cyclic GMP
keywords: Dexmedetomidine; Imidazoline receptor; Platelet; α(2)-Adrenoceptor