Effect of theophylline on beta-adrenergic receptor density and cAMP content in bovine aortic smooth muscle cells.
Activation of vascular beta-adrenergic receptors prevents an increase in vascular permeability caused by free radicals or inflammatory peptides. Methylxanthines seem to have similar protective effects on vascular endothelium. In the present study we investigated the effect of theophylline on the beta-adrenergic receptor expression and cAMP concentrations in cultured endothelial and smooth muscle cells from bovine aorta. Comparable values for beta-receptor density and binding affinity were detected in both cell types. Isoproterenol induced significant downregulation of beta-receptors in endothelial (BAEC: -60.5%) and smooth muscle cells (BASMC: -52.5%; P < 0.01). Incubation of endothelial cells with theophylline (4 micrograms/ml and and 40 micrograms/ml) for 24 hours did not affect beta-receptor expression, whereas in smooth muscle cells the beta-receptor density was reduced for -31.5% and -28.7%, respectively. In endothelial cells a transient effect on cAMP concentrations was observed after stimulation with isoproterenol (1 microM), but no effect was found in theophylline treated endothelial cells. Stimulation of intact smooth muscle cells with isoproterenol and theophylline (4 micrograms/ml and 40 micrograms/ml) resulted in a significant increase of cAMP concentrations after 60 and 240 minutes. The present data suggest a novel, celltype specific effect of theophylline on the beta-adrenergic receptor expression in vascular smooth muscle cells in vitro.
Graf
K
K
Department of Clinical Immunology and Asthma OPD, Virchow-Klinikum, Humboldt University, Berlin, Germany.
Dümmler
U
U
Grfe
M
M
O'Connor
A
A
Fleck
E
E
Kunkel
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D020120:Iodocyanopindolol; D010869:Pindolol; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol