The effects of histamine and prostaglandin D2 on rat mast-cell cyclic AMP and mediator release
The possibility that histamine may play a functional role in modulating mast-cell secretion, as has been suggested for basophil degranulation, has both physiologic and pharmacologic implications. Therefore the capacity of histamine to influence rat peritoneal mast-cell (RPMC) cyclic AMP levels and reversed anaphylatic degranulation as reflected in the release of 3H-serotonin (5-HT) was examined. To ascertain that RPMC were functionally responsive to exogenous hormonal stimulation, assessment of prostaglandin (PG) D2 effects on cyclic AMP and 5-HT release were determined in parallel. Although PGD2 (100 microM) increased cyclic AMP and inhibited 5-HT release in the presence of 50 microM aminophylline, histamine (up to 1000 microM) was ineffective was ineffective in both. However, 1000 microM histamine in the presence of 500 microM aminophylline was capable of transiently increasing RPMC cyclic AMP (for 15 to 30 sec) and under these conditions of suppressing 5-HT release. The receptor subtype involved in the suppressive actions of histamine appeared to be of the H-1 type as reflected in the capacity of specific H-1 agonists to reproduce the inhibition of 5-HT release, whereas neither H-2 agonists nor H-2 antagonists had any influence. Thus, under conditions in which phosphodiesterase enzymatic action is impaired, histamine in extremely high concentrations is able to modulate mast-cell secretion. However, it seems very unlikely that this action of histamine has any physiologic significance.
- Research Organization:
- Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD
- OSTI ID:
- 5394440
- Journal Information:
- J. Allergy Clin. Immunol.; (United States), Journal Name: J. Allergy Clin. Immunol.; (United States) Vol. 68:5; ISSN JACIB
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINES
AMP
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BIOCHEMISTRY
CHEMISTRY
CONNECTIVE TISSUE CELLS
DRUGS
HETEROCYCLIC COMPOUNDS
HISTAMINE
HYDROXY COMPOUNDS
IMIDAZOLES
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MAST CELLS
NEUROREGULATORS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHYSIOLOGY
PROSTAGLANDINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
RECEPTORS
RODENTS
SECRETION
SEROTONIN
SOMATIC CELLS
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES