The effect of a selective α2-adrenergic receptor antagonist (midaglizole) on the cyclic 3′,5′-adenosine monophosphate production in human mononuclear cells

Haruhito Sugiyama, Hidefumi Miyagawa, Chiharu Okada, Russell J. Hopp, Againdra K. Bewtra, Robert G. Townley

Research output: Contribution to journalArticle

Abstract

A selective α2-adrenergic antagonist, midaglizole, has been recently reported to have efficacy in patients with asthma. To understand the mechanisms, we investigated the effect of midaglizole on the cyclic 3′,5′-adenosine monophosphate (cAMP) production in human mononuclear cells (MNCs). MNCs were separated by a histopaque gradient from 10 normal subjects and 10 subjects with asthma. cAMP was measured by RIA kits. Midaglizole (10 μmol/L) significantly enhanced isoproterenol-induced cAMP production in both groups, although midaglizole (from 1 to 100 μmol/L) did not increase the cAMP production by itself. The percent increase in cAMP was more in subjects with asthma (183.8%) than in normal subjects (140.4%); however, the absolute increase was not different. Platelet-activating factor has been demonstrated to inhibit β-agonist-induced cAMP production in several mammalian tissues, including human MNCs. Midaglizole also prevented platelet-activating factor-induced desensitization of the cAMP response to isoproterenol in MNCs. These findings suggest that midaglizole may be a useful additional agent for the therapy of bronchial asthma through an enhancement of the cAMP production.

Original languageEnglish
Pages (from-to)722-729
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume89
Issue number3
DOIs
Publication statusPublished - 1992

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy

Cite this