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.
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)
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
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C013398:9-aminoacridylpropranolol; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol