Effects of Drugs on Mucus Glycoproteins and Water in Bronchial Secretion

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Abstract
The result of chemical analysis of the bronchial secretion is simple; up to 95% of the secretion is made up of water, and up to 5% is composed of ash, protein, carbohydrate, lipid, nitrogen and desoxyribonucleic acid. More complicated is the question of how bronchial secretion is formed and of which active biological components it is composed. Bronchial secretion is the result of the different processes, secretion, transudation, exudation and exfoliation from a highly differentiated bronchial mucosa. To those substances secreted belong, amongst others, constituents important for the flow properties and the transportability of the secretion: the bronchial mucus glycoproteins and water. The bronchial glycoproteins are the most important group, constituting 50–80% of the macromolecules. They are formed and secreted by the bronchial mucosa. The synthesis and secretion of bronchial glycoproteins are influenced by drugs in different ways. Beta-adrenergic stimulants do not alter these processes in in vitro studies on human glands, although an increase in mucus of glycoprotein production has been demonstrated in animal experiments and indirectly in man. Cyclic adenosine monophosphate and the methylxanthines stimulate mucus glycoprotein production, anticholinergic agents reduce but do not completely supress this process. Anti-allergic agents do not alter the production of bronchial glycoproteins with the exception of the corticosteroids which partially inhibit the synthesis and secretion. Neither expectorants nor mucolytic agents influence the production of mucus glycoproteins in human bronchial glands as opposed to animal experiments, in which these compounds produce an increase in the output of the bronchial fluid. Water constitutes 95% of the bronchial secretion and the water content considerably influences mucociliary function. An osmotic gradient, the result of active sodium and chloride ion transport across the bronchial epithelium, ensures on the one hand that water diffuses through epithelium on to the epithelial surface where it forms the serous sol layer in which the cilia beat. On the other hand water is probably transported in the same way across the mucosal glands where it mixes with the extremely hydrophilic mucus glycoproteins. The ion and water transport is influenced by drugs. Acetylcholine, histamine and terbutaline stimulate the ion and thereby water transport. Atropine, diphenylhydramine, an H1-antagonist, propranolol, a beta-blocker andfurosemide inhibit these transport mechanisms. Whether ketotifen, a new antihistaminic drug used in the treatment of bronchial asthma, will affect these processes, decreasing the water content of bronchial mucus, remains to be seen.