title: Regulation of beta-adrenergic receptors on endothelial cells in culture.
abstract: This study aimed to determine the density of vascular beta-adrenergic receptors in cultured endothelial cells and to study the regulation of endothelial receptors after exposure to catecholamines and the ACE inhibitors, lisinopril and ramiprilat. Membranes from bovine aortic endothelial cells (BAEC) and bovine pulmonary artery endothelial cells (BPAEC) showed saturable binding of the radioligand [125I]iodocyanopindolol (ICYP). The beta-receptor density and binding affinity were comparable in both types of endothelial cells. Isoproterenol induced significant down-regulation of beta-receptors (-50%; P < 0.01). Incubation (24h) with the ACE inhibitors lisinopril 10(-5) M (+28.8%; P < 0.05) and ramiprilat 10(-5) M (+33.7%, P < 0.09) augmented the beta-receptor density in BAEC, but lower ACE inhibitor doses had no affect. Incubation with lisinopril 10(-5) M for 24 h resulted in significantly lower cAMP baseline levels, but did not affect cAMP concentrations after stimulation with isoproterenol. These results indicate that down-regulation of endothelial beta-receptors occurs during prolonged exposure to beta-stimulation, and that high concentrations of ACE inhibitors may affect the density of endothelial beta-receptors.
authors.affiliation: Department of Internal Medicine and Cardiology, German Heart Institute, Berlin.
authors.forename: K
authors.initials: K
authors.lastname: Graf
authors.forename: M
authors.initials: M
authors.lastname: Gräfe
authors.forename: U
authors.initials: U
authors.lastname: Dümmler
authors.forename: A
authors.initials: A
authors.lastname: O'Connor
authors.forename: V
authors.initials: V
authors.lastname: Regitz-Zagrosek
authors.forename: G
authors.initials: G
authors.lastname: Kunkel
authors.forename: W
authors.initials: W
authors.lastname: Auch-Schwelk
authors.forename: E
authors.initials: E
authors.lastname: Fleck
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D017706:Lisinopril / Q000494:pharmacology; D011869:Radioligand Assay; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; C052549:ramiprilat; D000242:Cyclic AMP; D017706:Lisinopril; D017257:Ramipril; D007545:Isoproterenol