The beta-adrenergic receptor, its occupancy and subsequent modulation of intracellular cAMP, and mRNA expression were characterized for the promonocytic leukemia cell line THP-1. We report that THP-1 cells appear to express a beta-1 receptor with a Kd of 1.8 ± 0.3 × 10-11 μM and a B max of 108 ± 0.07 fmole/mg protein using 125I-iodocyanopindolol (125I-ICYP). The potency of various beta-adrenergic agonists to compete for the 125I-ICYP binding site followed the order: isoproterenol (0.8 μM)>dobutamine (2.1 μM)>salbutamol (3 μM)>epinephrine (3.8 μM)>soterenol) (4.6 μM)>terbutaline (11.1 μM)>norepinephrine (13.8 μM). Occupancy of the beta receptor on THP-1 cells results in activation of adenyl cyclase suggesting that these cells have a functional beta-adrenergic receptor. This receptor also has specific immunoregulatory properties, reducing message levels for tumor necrosis factor - but not interleukin 1, following treatment with isoproterenol (approximate EC-50 of 0.01 μM). We conclude, based on the above criteria, that THP-1 cells express a beta-1 receptor which, following ligand binding, results in increased cAMP leading to downregulation of TNF expression.
ASJC Scopus subject areas