Abstract
Ambroxol inhibits activity against phosphatidylcholine of phospholipase A from the lysosomes of rabbit lung, and in lysates of alveolar macrophages. The inhibition is of the same potency as that of imipramine and chloroquine. The latter are 2 of the many drugs with similar structural features, but very different pharmacologic actions, that can cause phospholipidosis in vivo as a result of the inhibition of lysosomal phospholipases. Since ambroxol shares these structural features, and inhibits the phospholipase A in vitro, we propose that the ability of ambroxol to elevate levels of pulmonary surfactant arises, at least in part, from this inhibitory property.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cerutti P, Kapanci Y (1979) Effects of metabolie VIII of bromexine (Na 872) on type II epithelium of the lung. An experimental and morphological study with reference to surfactant secretion. Respiration 37:241–251
Curti PC (1972) Steigerung der produktion der oberflächenaktiven substanzen der alveolen durch NA 872. Pneumonologie 147:62–74
Curti PC (1974) Therapeutische untersuchungen mit metabolit VIII von bromhexin bei mangelhafter oberflächenaktiver substanz der alveolen. Arzneim Forsch 24: 847–849
Dean RT, Jessup W, Roberts CR (1984) Effects of exogenous amines on mammalian cells, with particular reference to membrane flow. Biochem J 217:27–40
Eckert H, Lux M, Lachmann B (1983) The role of alveolar macrophages in surfactant turnover. An experimental study with metabolite VIII of Bromhexine (Ambroxol®). Lung 161:213–218
Gräbner R, Meerbach W (1983) Imipramine and chloroquine induced alterations in phospholipid content of rat lung. Exp Pathol 24:253–259
Heath MF, Jacobson W (1980) The action of lung lysosomal phospholipases on dipalmitoyl phosphatidylcholine and its significance for the synthesis of pulmonary surfactant. Pediatr Res 14:254–258
Heath MF, Jacobson W (1980) The nature of the phospholipases A of lung lamellar bodies. Pediatr Res 14:846–847
Heath MF, Jacobson W (1984) Developmental changes in enzyme activities in fetal and neonatal rabbit lung. Cytidylyltransferase, cholinephosphotransferase, phospholipases A1 and A2,β-galactosidase, andβ-glucuronidase. Pediatr Res 18:395–401
Heath MF, Jacobson W (1984) The effect of components of rabbit pulmonary surfactant on the activity of phospholipases. J Physiol (Lond) 346:439–448
Heath MF, Costa-Jussà FR, Jacobs JM, Jacobson W (1985) The induction of pulmonary phospholipidosis and the inhibition of lysosomal phospholipases by amiodarone. Br J Exp Pathol 66:391–398
Hollemans M, Oude Elferink R, de Groot PG, Strijland A, Tager JM (1981) Accumulation of weak bases in relation to intralysosomal pH in cultured human skin fibroblasts. Biochim Biophys Acta 643:140–151
Hostetler KY, Matsuzawa Y (1981) Studies on the mechanism of drug-induced lipidosis. Cationic amphiphilic drug inhibition of lysosomal phospholipases A and C. Biochem Pharmacol 30:1121–1126
Jacobs H, Jobe A, Ikegami M, Conaway D (1983) The significance of reutilization of surfactant phosphatidylcholine. J Biol Chem 258:4156–4165
Lüllmann-Rauch R (1979) Drug-induced lysosomal storage disorders. In: Dingle JT, Jacques PJ, Shaw IH (eds) Lysosomes in applied biology and therapeutics, vol 6. North-Holland Publ. Co., Amsterdam, pp 49–129
Marchlinski FE, Gansler TS, Waxman HL, Josephson ME (1982) Amiodarone pulmonary toxicity. Ann Intern Med 97:839–845
Matsuzawa Y, Hostetler KY (1980) Inhibition of lysosomal phospholipase A and phospholipase C by chloroquine and bis(diethylaminoethyl)α,β-diethyldiphenylethane. J Biol Chem 255:5190–5194
Post M, Batenburg JJ, Schuurmans EAJM, Oldenborg V, van der Molen AJ, van Golde LMG (1983) The perfused rat lung as a model for studies on the formation of surfactant and the effect of Ambroxol on this process. Lung 161:349–359
Prévost MC, Soula G, Douste-Blazy L (1978) Effect of bromhexine metabolite on the phospholipids of rabbit pulmonary macrophages. Bull Eur Physiopathol Respir 14:53–60
Prévost MC, Soula G, Douste-Blazy L (1979) Biochemical modifications of pulmonary surfactant after bromhexine derivative injection. Respiration 37:215–219
Reasor MJ, Heyneman CA (1983) Disaturated phosphatidylcholine in the pulmonary airspaces of rats treated with chlorphentermine. Biochem Pharmacol 32:939–941
Sgaragli GP, della Corte L, Gremigni D (1983) Chlorimipramine-induced phospholipidosis: biochemical and pharmacokinetic observations in the rat. Pharmacol Res Commun 15:231–246
Stern N, Tietz A, Gaton E, Wolman M (1983) Effects of chlorocyclizine on pulmonary lipid metabolism in rats. Biochim Biophys Acta 754:166–173
van Golde LMG (1976) Metabolism of phospholipids in the lung. Am Rev Respir Dis 114:977–1000
van Petten GR, Mears GJ, Taylor PJ (1978) The effects of NA 872 on pulmonary maturation in the fetal lamb and rabbit. Am J Obstet Gynecol 130:35–40
Velásquez Sepúlveda J (1982) Influence of transplacental NA-872 and dexamethasone therapy on fetal and newborn mouse lung. Respiration 43:389–400
Wauer RR, Schmalisch G, Menzel K, Schröder M, Müller K, Tiller R, Methfessel G, Sitka U, Koepke E, Plath C, Schlegel C, Böttcher M, Köppe I, Fricke U, Severin K, Jacobi R, Schmidt W, Hinkel GK, Nitz I, Kunze D, Reichmann G, Lachmann B, Lampe K, Grauel EL (1982) The antenatal use of ambroxol (bromhexine metabolite VIII) to prevent hyaline membrane disease—a controlled double-blind study. Int J Biol Res Pregnancy 3:84–91
Zeligs BJ, Zeligs JD, Nerurkar LS, Bellanti JA (1977) Maturation of the rabbit alveolar macrophage during animal development. 1. Perinatal influx into alveoli and ultrastructural differentiation. Pediatr Res 11:197–208
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Heath, M.F., Jacobson, W. The inhibition of lysosomal phospholipase A from rabbit lung by ambroxol and its consequences for pulmonary surfactant. Lung 163, 337–344 (1985). https://doi.org/10.1007/BF02713834
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02713834