Molecular pharmacology of the beta-adrenergic receptor on THP-1 cells

James E Talmadge, Robert Scott, Paola Castelli, Tonie Newman-Tarr, John Lee

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)219-228
Number of pages10
JournalInternational Journal of Immunopharmacology
Volume15
Issue number2
DOIs
StatePublished - Jan 1 1993

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Receptors, Adrenergic, beta
Iodocyanopindolol
Pharmacology
Isoproterenol
Terbutaline
Adrenergic beta-Agonists
Dobutamine
Albuterol
Interleukin-1
Adenylyl Cyclases
Epinephrine
Norepinephrine
Leukemia
Down-Regulation
Tumor Necrosis Factor-alpha
Binding Sites
Ligands
Cell Line
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Molecular pharmacology of the beta-adrenergic receptor on THP-1 cells. / Talmadge, James E; Scott, Robert; Castelli, Paola; Newman-Tarr, Tonie; Lee, John.

In: International Journal of Immunopharmacology, Vol. 15, No. 2, 01.01.1993, p. 219-228.

Research output: Contribution to journalArticle

Talmadge, James E ; Scott, Robert ; Castelli, Paola ; Newman-Tarr, Tonie ; Lee, John. / Molecular pharmacology of the beta-adrenergic receptor on THP-1 cells. In: International Journal of Immunopharmacology. 1993 ; Vol. 15, No. 2. pp. 219-228.
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