Mechanistic aspects of cromolyn sodium action on the alveolar macrophage: Inhibition of stimulation by soluble agonists

A. Holian, R. Hamilton, R. K. Scheule

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Despite wide use of the drug cromolyn sodium, its mechanism of action remains unknown. The alveolar macrophage plays a major role in the regulation of the inflammatory responses of the lung which may contribute to asthma. Since the biochemical mechanism by which agonists stimulate the alveolar macrophage to produce superoxide anion has been described, the effects of cromolyn sodium on this process were examined. Cromolyn sodium (0.5-4 m M) reversibly blocked macrophage stimulation by formyl peptide and leukotriene B4, but not by phorbol diester and concanavalin A. Cromolyn sodium inhibition was not calcium dependent and could be reversed by increasing the dose of agonist. Cromolyn sodium did not elevate intracellular cAMP, nor did the characteristics of inhibition resemble those observed using cAMP to inhibit agonist stimulation. However, cromolyn sodium did block agonist-mediated stimulation of the phosphatidylinositol (PI) pathway. Taken together, the present results suggest that one site of action of cromolyn sodium may be at the GTP-binding protein of the PI pathway.

Original languageEnglish
Pages (from-to)318-325
Number of pages8
JournalAgents and Actions
Volume33
Issue number3-4
DOIs
StatePublished - Jul 1991

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