Localization of quantitative changes in pulmonary beta-receptors in ovalbumin-sensitized guinea pigs.
Impaired beta-receptor function has been postulated as one factor contributing to airway hyperreactivity in asthmatic patients. Although numerous indirect studies have cast doubt on this theory, none of these previous investigations has been able to directly measure changes in beta-receptor number on intrapulmonary structures capable of affecting the physiologic changes seen in this disease state. To help clarify the intrapulmonary location of such changes, a model of allergic bronchoconstriction was prepared by sensitizing guinea pigs to ovalbumin intraperitoneally (ip) 2 wk prior to testing (Group S). A second group of animals was sensitized to ovalbumin, then 2 wk later partially desensitized (Group D) during a 4- to 6-wk period by repeated exposure to increasing doses of nebulized ovalbumin with epinephrine rescue. Control animals received ip administered and nebulized normal saline alone. Pulmonary function assessed by plethysmography revealed an increase in airway resistance to 294 +/- 42% (SE) of control in Group S (p less than 0.005) and a decrease in dynamic compliance to 76 +/- 8% of control in Group D and 39 +/- 10% of control in Group S (p less than 0.002) after exposure to nebulized ovalbumin. Using L-[3H] dihydroalprenolol ([3H] DHA), beta-receptors were autoradiographically localized and quantitated in lung sections from all 3 groups. Significant decreases (p less than 0.02) in 3H-DHA binding were noted in alveolar and conducting airway epithelium, and bronchiolar and vascular smooth muscle in ovalbumin-exposed animals.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001345:Autoradiography; D004082:Dihydroalprenolol / Q000378:metabolism; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D007114:Immunization / Q000379:methods; D008168:Lung / Q000032:analysis* / Q000503:physiopathology; D010047:Ovalbumin / Q000276:immunology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D011943:Receptors, Adrenergic, beta; D014316:Tritium; D004082:Dihydroalprenolol; D010047:Ovalbumin