In vitro studies on the relative potency of bronchodilator agents |
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Authors: | Joseph H Fleisher Jacob L Pinnas |
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Institution: | (1) Department of Internal Medicine, Arizona Health Sciences Center, 85724 Tucson, Arizona, USA |
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Abstract: | This study describes a rapid in vitro assay for the order of potency of bronchodilator drugs using specific binding of (−)-3H] dihydroalprenolol (3H]DHA) to rat lung membranes. Under linear conditions with respect to tissue, specific binding of 3H]DHA showed saturability, rapid kinetics of association and dissociation of radioligand, and sterospecificity. Nanomolar
(nM) concentrations for 50% inhibition (IC50±SE) for the bronchodilator drugs examined were as follows: albuterol, 1485±170; isoproterenol, 136±53; procaterol, 162±28;
terbutaline, 3310±934; and zinterol, 51±8.3. A comparison of binding studies using rat lung tissue membranes and similar preparations
of rat heart and skeletal muscle demonstrated that lung tissue had 7 to 8 times more receptor sites (Bmax) for 3H]DHA than heart or skeletal muscle. Adenyl cyclase activit of the rat lung membrane preparation almost doubled in the presence
of (−)-isoproterenol. Displacement of specific (3H)DHA binding in membrane preparations may provide useful data for evaluating bronchodilator compounds. |
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Keywords: | [3H] Dihydroalprenolol Beta-adrenergic bronchodilator compounds Rat lung membranes Adenylate cyclase activity Cyclic adenosine monophosphate (cAMP) |
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