Beta 2-adrenergic receptors on eosinophils. Binding and functional studies

Journal Article · Fri Jun 01 04:00:00 EDT 1990 · American Review of Respiratory Disease (New York); (USA)

DOI:https://doi.org/10.1164/ajrccm/141.6.1446· OSTI ID:6718386

Yukawa, T; Ukena, D; Kroegel, C; Chanez, P; Dent, G; Chung, K F; Barnes, P J ^[1]

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1. National Heart and Lung Institute, Brompton Hospital, London (England)

We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand (125I)pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed.

• OSTI ID: 6718386
• Journal Information: American Review of Respiratory Disease (New York); (USA), Journal Name: American Review of Respiratory Disease (New York); (USA) Vol. 141:6; ISSN ARDSB; ISSN 0003-0805
• Country of Publication: United States
• Language: English

Related Subjects

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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMP
ANIMALS
ASTHMA
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CYCLASES
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
ESTERS
FUNCTIONS
GUINEA PIGS
IN VITRO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LEUKOCYTES
LYASES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
NEUTROPHILS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATHOGENESIS
PERITONEUM
PEROXIDASES
PHORBOL ESTERS
PRIMATES
PROTEINS
RADIOASSAY
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RESPIRATORY SYSTEM DISEASES
RODENTS
SEROUS MEMBRANES
SYMPATHOMIMETICS
TRACER TECHNIQUES
VERTEBRATES
ZYMOSAN