Pathogenetic Mechanisms of Bronchial Asthma and Airway Hyperresponsiveness: A Pharmacological View. Role of peptide-leukotrienes in bronchial asthma

Peptide-leukotrienes (p-LTs) (LTC4, LTD4 and LTE4) are major metabolites of the arachidonate 5-lipoxygenase pathway. Although a number of papers have reported that p-LTs induce potent bronchial smooth muscle constriction as well as airway mucus secretion, vascular permeability and proliferation of airway smooth muscle cells, it had not been recognized that they are pivotal chemical mediators in asthmatic diseases until recently. Yet, several potent and selective antagonists against p-LTs and inhibitors of p-LT formation revealed that p-LTs play significant roles in not only allergic but non-allergic asthma including exercise- and aspirin-induced asthma. In addition, it has been reported that p-LTs participate in rhinitis, especially nasal blockage. In this article, recent development of drugs relating to p-LTs and their therapeutic effects for asthma are mainly reviewed.