title: Interactions of beta adrenergic antagonists with isolated rat alveolar type II pneumocytes. II. Receptor-independent accumulation of beta adrenergic antagonists and other cationic amphiphilic drugs in lamellar bodies.
abstract: Accumulation of basic drugs by pulmonary tissue is well known. The cationic amphiphilic nature of many of these compounds suggests that they may be sequestered within an acidic and/or phospholipid-rich compartment. We described previously receptor-independent, concentrative, temperature- and pH-dependent sequestration of the beta adrenergic antagonists [125I]iodocyanopindolol and [125I]iodopindolol by intact rat type II pneumocytes in primary culture. The present study reveals that type II pneumocytes sequester [125I]iodocyanopindolol to an extent greater than other cell types (type II cells greater than polymorphonuclear leukocytes greater than S49) within 80-min incubations. Localization of fluorescence into large granular structures was observed after incubation of type II cells with 9-aminoacridine-propranolol (9-AAP). The distribution of fluorescence coincides with surfactant-containing lamellar bodies (LB) visualized with tannic acid/osmium staining. The large granule localization of 9-AAP fluorescence decreases with time in primary culture in parallel with changes in cell morphology and decreased numbers of LB. Comparison of patterns of fluorescence after incubation with 9-AAP, acridine orange and 9-aminoacridine (all 1 microM) indicates that localization is not a property of the acridine moiety, but requires the propranolol side-chain. Association of 9-AAP fluorescence with LB is inhibited completely by chlorpromazine (10 microM); the same concentration of propranolol or chlorquine produces less extensive, but detectable, inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D006651:Histocytochemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020120:Iodocyanopindolol; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011433:Propranolol / Q000031:analogs & derivatives / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013696:Temperature
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C013398:9-aminoacridylpropranolol; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol