Desmopressin stimulates the expression of P-selectin on human platelets in vitro.
Desmopressin (1-desamino-8-D-arginine vasopressin (DDAVP)) is a synthetic analog of arginine vasopressin (AVP) and is useful in the treatment of some bleeding disorders. The mechanism of improved hemostasis in patients with platelet dysfunction is uncertain. Platelet-rich plasma samples from 35 normal subjects were incubated with serial dilutions of DDAVP, AVP, and adenosine diphosphate. The expression of the platelet activation-dependent antigen CD62 (P-selectin) was measured by fluorescent-labeled monoclonal antibody and flow cytometry. DDAVP at concentrations of 1.0 to 1000 nmol/L stimulated significant expression of CD62 on normal platelets in vitro. At a pharmacologic concentration of DDAVP (1 nmol/L), 14.1% (0.6% to 45.4%) (median and range) of platelets expressed CD62. There was a strong correlation between DDAVP-induced and AVP-induced CD62 expression (rs = 0.62, p = 0.0008) but not between DDAVP-induced and ADP-induced expression, suggesting a V1 receptor-mediated mechanism. Preincubation of platelets with a vasopressin V1 receptor antagonist completely inhibited CD62 expression in response to DDAVP. We conclude that DDAVP directly activates platelets by interaction with the platelet V1 receptor in vitro. This finding may partially explain in vivo effects of DDAVP on hemostasis.
Wun
T
T
University of California Davis Cancer Center, UC Davis School of Medicine, Sacramento 95817, USA.
Paglieroni
T G
TG
Lachant
N A
NA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D065092:Antidiuretic Hormone Receptor Antagonists; D015703:Antigens, CD / Q000096:biosynthesis* / Q000097:blood; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004148:Dioxolanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006487:Hemostasis; D006801:Humans; D066298:In Vitro Techniques; D019007:P-Selectin / Q000096:biosynthesis* / Q000097:blood
D000911:Antibodies, Monoclonal; D065092:Antidiuretic Hormone Receptor Antagonists; D015703:Antigens, CD; D004148:Dioxolanes; D019007:P-Selectin; D001127:Arginine Vasopressin; D000244:Adenosine Diphosphate; D003894:Deamino Arginine Vasopressin; C010962:formal glycol