title: Deficient elevation of the cytoplasmic calcium ion concentration by epinephrine in epinephrine-insensitive platelets of patients with myeloproliferative disorders.
abstract: Elevation of the cytoplasmic Ca2+ concentration ([Ca2+]i) by epinephrine and epinephrine-induced inhibition of prostaglandin E1 (PGE1)-stimulated cyclic adenosine monophosphate (cAMP) accumulation were assessed in platelets from three groups of subjects; normal controls (NS, n = 11) and patients with myeloproliferative disorders whose platelets were either sensitive (ES, n = 9) or specifically insensitive (El, n = 7) to the aggregatory effect of epinephrine. The inhibition by epinephrine of cAMP accumulation in the platelets exposed to 500 nM PGE1 was not significantly different between the three groups. Therefore, despite the defective aggregation response to epinephrine, platelets from the El group seemed to retain normal response, which was attained through alpha 2-adrenergic receptors, guanine nucleotide binding regulatory protein, and the adenylate cyclase system. However, in aequorin-loaded, washed platelets, the epinephrine-stimulated rise in [Ca2+]i showed significant decrease in the El group compared with the other groups (P less than 0.01). Thus the mechanism for the impaired aggregation response to epinephrine in platelets from the El group could include the defect that exists in the pathway from receptor binding of epinephrine to the aggregation response through [Ca2+]i elevation.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Ushikubi
authors.forename: M
authors.initials: M
authors.lastname: Okuma
authors.forename: T
authors.initials: T
authors.lastname: Ishibashi
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
authors.forename: H
authors.initials: H
authors.lastname: Uchino
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D000242:Cyclic AMP / Q000097:blood; D003593:Cytoplasm / Q000378:metabolism*; D004351:Drug Resistance; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D009196:Myeloproliferative Disorders / Q000097:blood*; D009994:Osmolar Concentration; D010974:Platelet Aggregation
chemical_list: D000242:Cyclic AMP; D002118:Calcium; D004837:Epinephrine