The effect of a selective alpha 2-adrenergic receptor antagonist (midaglizole) on the cyclic 3',5'-adenosine monophosphate production in human mononuclear cells.
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| Abstract |
A selective alpha 2-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 mumol/L) significantly enhanced isoproterenol-induced cAMP production in both groups, although midaglizole (from 1 to 100 mumol/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 beta-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.
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| Authors | H Sugiyama, H Miyagawa, C Okada, R J Hopp, A K Bewtra, R G Townley |
| Journal | The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 89 Issue 3 Pg. 722-9 (Mar 1992) ISSN: 0091-6749 [Print] United States |
| PMID | 1347546 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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