Inhibition of low pH evoked activation of airway sensory nerves by capsazepine, a novel capsaicin-receptor antagonist

• Published in: Biochemical and biophysical research communications Vol. 189; no. 1; pp. 537 - 544
• Main Authors: Lou, Ya-Ping, Lundberg, Jan M.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 30.11.1992; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcitonin Gene-Related Peptide - metabolism; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Citrates - pharmacology; Citric Acid; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Hydrogen-Ion Concentration; In Vitro Techniques; Isolated neuron and nerve. Neuroglia; Lung - drug effects; Lung - innervation; Lung - physiology; Neurokinin A - metabolism; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Nicotine - pharmacology; Receptors, Drug - antagonists & inhibitors; Respiratory Physiological Phenomena; Respiratory System - drug effects; Ruthenium Red - pharmacology; Tidal Volume - drug effects; Vagus Nerve - physiology; Vertebrates: nervous system and sense organs; NKA; CGRP; LI; R L; Capsaicin; Secretion; Lung; Rodentia; Competitive inhibition; Vertebrata; Bronchoconstriction; Sensitivity; Mammalia; Guinea pig; Neuromedin L; Sensory nerve; Antagonist; Acid medium; Biological receptor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(92)91591-D

Low pH is a well known sensory irritant in pathological conditions such as inflammation. The mechanisms underlying this low pH effect were therefore studied in the guinea pig. Acid exposure caused marked nasal irritation via a specific subset of sensory nerves sensitive to capsaicin. Futhermore, acid caused bronchoconstriction via release of neuropeptides from capsaicin sensitive afferents. Interestingly, capsazepine, a recently developed competitive capsaicin receptor antagonist, selectively inhibited these responses to low pH. Ruthenium red, which blocks the cation channel associated with the capsaicin receptor, had effects similar to those of capsazepine. Therefore, acid irritation of the airway mucosa may involve capsaicin-receptor mechanisms and capsazepine represents a novel protective agent.