Faculty Collaboration Database

Enhancement of the antiaggregatory activity of prostacyclin by propranolol in human platelets. Circulation 1985 Jun;71(6):1237-46

Date

06/01/1985

Pubmed ID

2986877

DOI

10.1161/01.cir.71.6.1237

Scopus ID

2-s2.0-0021815741 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

The beta-adrenergic antagonist propranolol has been found to inhibit platelet aggregation. We investigated the possibility that propranolol exerts this action by stimulating the synthesis or enhancing the antiaggregatory activity of prostaglandin (PG) I2. The media from cultures of human endothelial cells inhibited thrombin-induced platelet aggregation, an effect attributed to PGI2 production by the cells. When endothelial cells were incubated with dl- or d-propranolol, the media had two to three times the inhibitory activity of control media. However, this increased activity was not due to increased synthesis of PGI2 because control and propranolol-treated cultures synthesized similar amounts of the PGI2 metabolite, 6-keto-PGF1 alpha. Instead, propranolol enhanced the antiaggregatory activity of PGI2. Propranolol (1 microM) and PGI2 (0.05 nM), when tested separately, inhibited aggregation by 19% and 13%, respectively, whereas the combination inhibited aggregation by 51%. PGI2 inhibited platelet aggregation and thromboxane (Tx) B2 production but stimulated cyclic AMP formation. The adenyl cyclase inhibitor 2',5'-dideoxyadenosine (DDA) had no effect of its own on these parameters, but blocked the actions of PGI2. Propranolol inhibited aggregation and TxB2 synthesis without changing cyclic AMP levels. Unlike PGI2, propranolol's effects were not altered by DDA. While the combination of propranolol and PGI2 inhibited aggregation to a greater extent than either agent alone, this enhanced effect with the combination did not extend to TxB2 or cyclic AMP production. Propranolol, PGI2, and the combination inhibited TxB2 synthesis to a similar extent, and PGI2 produced a similar increase in cyclic AMP in the presence and absence of propranolol. These findings indicate that propranolol and PGI2 inhibit platelet aggregation through cyclic AMP-independent and dependent mechanisms, respectively. While propranolol does not alter the synthesis of PGI2, it enhances the inhibition of aggregation by PGI2, and this may contribute to its antiplatelet effect.

Author List

Callahan KS, Johnson AR, Campbell WB

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cells, Cultured
Cyclic AMP
Deoxyadenosines
Dideoxyadenosine
Drug Synergism
Endothelium
Epoprostenol
Humans
In Vitro Techniques
Platelet Aggregation
Propranolol
Thromboxane B2