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Influence of trifluoperazine on platelet aggregation and disaggregation. 1980

G H Rao, and K R Reddy, and J G White

Calmodulin has been shown to activate platelet phospholipase A2 and initiate the metabolism of arachidonic acid. Trifluoperazine (stelazine), an agent which selectively binds calmodulin, inhibits phospholipase activity induced by calcium. We have evaluated the effect of this agent on the aggregation, disaggregation and reaggregation of human platelets. Results of our study have shown that stelazine is a selective inhibitor of the second wave response of platelets to the stimulation of agonists. The compound causes dissociation of aggregated platelet clumps and induces a refractory state in dispersed cells. Epinephrine reverses the refractory state and potentiates the response of dissociated cells to the action of thrombin, arachidonate and ionophore A23187. Stelazine elevates cAMP levels to some extent and inhibits release of labeled arachidonic acid from platelet membranes in response to thrombin induced stimulation. Epinephrine may correct stelazine induced inhibition by acting through alpha-adrenergic mechanism, by inducing changes in membrane permeability to calcium, by releasing membrane associated calcium or by directly promoting deacylation of phospholipids.

UI MeSH Term Description Entries
D010741 Phospholipases A Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D004837 Epinephrine The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS. Adrenaline,4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol,Adrenaline Acid Tartrate,Adrenaline Bitartrate,Adrenaline Hydrochloride,Epifrin,Epinephrine Acetate,Epinephrine Bitartrate,Epinephrine Hydrochloride,Epinephrine Hydrogen Tartrate,Epitrate,Lyophrin,Medihaler-Epi,Acetate, Epinephrine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D001095 Arachidonic Acids Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D014268 Trifluoperazine A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic. Trifluoroperazine,Triftazin,Apo-Trifluoperazine,Eskazine,Flupazine,Stelazine,Terfluzine,Trifluoperazine HCL,Trifluoperazine Hydrochloride,Trifluperazine,Apo Trifluoperazine,ApoTrifluoperazine
D054467 Phospholipases A2 Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES. Lecithinase A2,Phospholipase A2

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