Cyclic AMP agonist inhibition increases at low levels of histamine release from human basophils
The relationship between the intensity of the signal for antigen-induced immunoglobulin E-mediated histamine release from human basophils and the concentration of agonist needed to inhibit release has been determined. The agonists, prostaglandin E1, dimaprit, fenoterol, isobutylmethylxanthine and dibutyryl cyclic AMP, all act by increasing the cyclic AMP level. Each agonist was 10- to 1000-fold more potent (relative ID50) at low levels of histamine release (5-10% of total histamine) than at high levels (50-80%). Thus, the inhibitory potential of a drug is a function of the concentration of antigen used to initiate the response. Our results are now more in accord with the inhibitory profile of these drugs in human lung tissue. It is suggested that in vivo release is likely to be low and that this is the level at which to evaluate drugs in vitro.
- OSTI ID:
- 5467645
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 218:3; ISSN JPETA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
551000 -- Physiological Systems
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMP
ANTIGEN-ANTIBODY REACTIONS
AZOLES
BASOPHILS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
COMPARATIVE EVALUATIONS
DRUGS
HETEROCYCLIC COMPOUNDS
HISTAMINE
IMIDAZOLES
IMMUNITY
KINETICS
LEUKOCYTES
LUNGS
MATERIALS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PH VALUE
QUANTITY RATIO
REACTION KINETICS
RESPIRATORY SYSTEM