Isoproterenol antagonizes endothelial permeability induced by thrombin and thrombin receptor peptide.
We determined whether 1) amino-terminal peptides of the thrombin receptor increase endothelial permeability to a comparable extent as alpha-thrombin does, 2) isoproterenol attenuates the thrombin-induced increase in endothelial permeability by an antagonistic action to that of thrombin or by lowering baseline permeability, and 3) isoproterenol decreases permeability via stimulation of the beta 2-adrenergic receptor. Permeability across monolayers of bovine pulmonary artery endothelial cells (CCL 209) was assessed by the clearance of 125I-labeled albumin. Thrombin receptor peptides increased permeability at 1 microM but required a dose of between 10 and 100 microM to equal the permeability response of 1 microM alpha-thrombin. Dose-response experiments demonstrated that isoproterenol antagonized the action of alpha-thrombin and a thrombin receptor peptide on endothelial permeability and that it lowered baseline permeability. This permeability-decreasing action of isoproterenol occurred via stimulation of the beta 2-adrenergic receptor. Terbutaline, a partial beta 2-agonist, prevented the thrombin-induced permeability, but dobutamine, a partial beta 1-agonist, did not. The active stereoisomer of terbutaline and the racemic form mimicked the action of isoproterenol, but the inactive stereoisomer had no effect. ICI-118,551, a specific beta 2-receptor antagonist, prevented the permeability-decreasing action of isoproterenol, whereas ICI-89,406, a specific beta 1-receptor antagonist, did not. Competitive binding studies of 125I-pindolol with ICI-118,551 or ICI-89,406 demonstrated the presence of beta-adrenergic receptors, predominantly beta 2-receptors, on cell membrane homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)
Minnear
F L
FL
Department of Physiology and Cell Biology, Albany Medical College of Union University, New York 12208.
DeMichele
M A
MA
Leonhardt
S
S
Andersen
T T
TT
Teitler
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002199:Capillary Permeability / Q000187:drug effects*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D018179:Receptors, Thrombin / Q000737:chemistry*; D013917:Thrombin / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D010446:Peptide Fragments; D018179:Receptors, Thrombin; D013917:Thrombin; D007545:Isoproterenol