Uncoupling of the beta-adrenergic receptor as a mechanism of in vitro neutrophil desensitization

Journal Article · Wed Feb 01 04:00:00 EST 1984 · J. Lab. Clin. Med.; (United States)

OSTI ID:6630926

Galant, S P; Britt, S

Human leukocytes have been useful in studying desensitization phenomena to beta-adrenergic agonists in a number of clinical conditions. In the present in vitro study the authors have explored the mechanism for beta-adrenergic desensitization and have compared conditions for homologous and heterologous desensitization, using the intact PMN model. PMN preincubated with isoproterenol (10/sup -4/M), washed thoroughly, then restimulated, desensitized rapidly so that within 10 min 80% of control isoproterenol-induced cyclic AMP stimulation is lost. Cells washed free of isoproterenol recover full responsiveness in 1 to 2 hr. The estimated isoproterenol desensitization EC/sub 50/ in cells washed and then restimulated is 1 x 10/sup -5/M, and EC/sub 50/ in unwashed cells that are restimulated is 9 x 10/sup -8/M. Rank-order potency studies of catecholamine desensitization show isoproterenol > epinephrine > norepinephrine, a beta-2 pattern. Isoproterenol-induced desensitization results in a small reduction in (/sup 3/H)DHA binding sites, which becomes statistically significant (p < 0.05) from control values at 1 hr (67% of control) and 3 hr (64%). In the absence of GTP, isoproterenol binding is characterized by an EC/sub 50/ of 6.6 +/- 2.6 x 10/sup -/(M, which is significantly different (p < 0.05) from the EC/sub 50/ of 38.1 +/- 9.1 x 10/sup -1/M found when cells are previously desensitized with isoproterenol for 10 min. GTP does not affect the EC/sub 50/ of desensitized cells. Finally, prolonged (3 hr) isoproterenol preincubation results in a small but significant (p < 0.05) loss of cyclic AMP responsiveness to histamine (67.7% +/- 11.7 of control) and PGE/sub 1/ (59.3% +/- 7.4), suggesting heterologous desensitization. These studies suggest that the human PMN is a suitable model to study both homologous and heterologous desensitization in vitro. 22 references. 6 figures. 3 tables.

• Research Organization: Memorial Hospital Medical Center, Long Beach, CA
• OSTI ID: 6630926
• Journal Information: J. Lab. Clin. Med.; (United States), Journal Name: J. Lab. Clin. Med.; (United States) Vol. 103:2; ISSN JLCMA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ADRENALINE
AMP
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
DRUGS
HORMONES
HYDROGEN ISOTOPES
IN VITRO
ISOTOPE APPLICATIONS
ISOTOPES
LABELLING
LEUKOCYTES
LIGHT NUCLEI
LOSSES
MAMMALS
MAN
MATERIALS
MATHEMATICAL MODELS
NEUROREGULATORS
NEUTROPHILS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
RADIOISOTOPES
RECEPTORS
SENSITIVITY
STEROID HORMONES
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM
VERTEBRATES
YEARS LIVING RADIOISOTOPES