Purines and sensory neuropeptides in human asthma.
Mediators acting on different cells in the lung may produce features of asthma such as bronchoconstriction, plasma leakage from the tracheobronchial microcirculation and mucus secretion. The clinical effectiveness of anticholinergic agents has stimulated the search for mediators other than acetyolcholine and the hope that specific antagonists would improve asthma therapy. The purine, nucleoside adenosine, produces certain asthma-like signs such as bronchoconstriction in asthmatics. Studies with theophylline and nonadenosine-blocking bronchodilator xanthines have, however, demonstrated that adenosine is unlikely to be an asthma mediator, although it may still possess significant extrapulmonary actions. Sensory nerves within the lung show immunoreactivity to a wide variety of peptides, including substance P and other tachykinins. Tachykinins produce bronchoconstriction and plasma extravasation in guinea-pig and rat lungs. In asthmatic subjects, nebulized neurokinin A reduces specific airways conductance. Inhalation of capsaicin, which presumably acts through stimulation of chemosensitive afferent C-fibres, produces cough and a transient upper airway constriction. Elucidation of a role in asthma must await the development of a clinically useful tachykinin antagonist. Accumulating data seems to indicate that asthma pathology is caused by released substances acting in conjunction on target cells in the lung. Functional antagonism, rather than inhibition of a single mediator, thus appears to be essential for clinically effective antiasthma drugs.
Karlsson
J A
JA
AB Draco, Lund, Sweden.
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009479:Neuropeptides / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D018039:Receptors, Tachykinin; D015320:Tachykinins
D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D018039:Receptors, Tachykinin; D015320:Tachykinins; D000241:Adenosine