Regulation of human mast cell and basophil function by cAMP.
1. Mast cells and basophils are important in mediating allergic disorders such as asthma. Activation of these cells results in the release of a wide variety of mediators that can promote inflammatory responses. 2. Receptor-mediated activators of adenylate cyclase such as the beta-adrenoceptor agonist, isoprenaline, and prostaglandin E2 (PGE2) are effective at inhibiting mediator release from human lung mast cells (HLMC) but not basophils. In HLMC, both isoprenaline and PGE2 elevate and sustain increases in cyclic adenosine 3',5'-monophosphate (cAMP) whereas in basophils, both compounds cause transient increases in cAMP. 3. Non-selective inhibitors of phosphodiesterase (PDE) such as theophylline and 3-isobutyl-1-methylxanthine are effective inhibitors of mediator release from both HLMC and basophils and both compounds cause elevations of cAMP that are sustained in both cell types. 4. Studies with selective inhibitors of PDE indicate that the cAMP-specific PDE, PDE 4, regulates the activity of basophils but not HLMC. The nature of the PDE regulating HLMC responses is uncertain. 5. These data indicate that agents that induce and sustain elevations in intracellular cAMP attenuate the stimulated release of mediators from mast cells and basophils. However, the responsiveness of HLMC and basophils to selected cAMP-active agents differs.
Weston
M C
MC
Section of Molecular Pharmacology and Pharmacogenetics, University of Sheffield, The Royal Hallamshire Hospital.
Peachell
P T
PT
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001491:Basophils / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP