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 language | English |
|---|---|
| Pages (from-to) | 722-729 |
| Number of pages | 8 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 89 |
| Issue number | 3 |
| DOIs | |
| State | Published - 1992 |
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All Science Journal Classification (ASJC) codes
- Immunology
- Immunology and Allergy
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The effect of a selective α2-adrenergic receptor antagonist (midaglizole) on the cyclic 3′,5′-adenosine monophosphate production in human mononuclear cells. / Sugiyama, Haruhito; Miyagawa, Hidefumi; Okada, Chiharu; Hopp, Russell J.; Bewtra, Againdra K.; Townley, Robert G.
In: Journal of Allergy and Clinical Immunology, Vol. 89, No. 3, 1992, p. 722-729.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The effect of a selective α2-adrenergic receptor antagonist (midaglizole) on the cyclic 3′,5′-adenosine monophosphate production in human mononuclear cells
AU - Sugiyama, Haruhito
AU - Miyagawa, Hidefumi
AU - Okada, Chiharu
AU - Hopp, Russell J.
AU - Bewtra, Againdra K.
AU - Townley, Robert G.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
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U2 - 10.1016/0091-6749(92)90380-K
DO - 10.1016/0091-6749(92)90380-K
M3 - Article
VL - 89
SP - 722
EP - 729
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -