The effect of a selective alpha 2-adrenergic receptor antagonist (midaglizole) on the cyclic 3',5'-adenosine monophosphate production in human mononuclear cells.
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.
Sugiyama
H
H
Creighton University, Allergic Disease Center, Omaha, NE 68178.
Miyagawa
H
H
Okada
C
C
Hopp
R J
RJ
Bewtra
A K
AK
Townley
R G
RG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D001249:Asthma / Q000097:blood; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D010972:Platelet Activating Factor; C032368:midaglizole; D000242:Cyclic AMP; D007545:Isoproterenol