Release of Multiple Tachykinins from Capsaicin-sensitive Sensory Nerves in the Lung by Bradykinin, Histamine, Dimethylphenyl Piperazinium, and Vagal Nerve Stimulation

Abstract

Recent evidence suggests that activation of airway C-fibers, besides causing afferent transmission, also causes release of transmitters from peripheral endings, probably via local axons reflexes, resulting in effects on vascular and bronchial smooth muscle, i.e., vasodilatation, increase in vascular permeability, and bronchoconstriction. In the present study, the release of tachykinins was investigated in the perfused guinea pig lung by various ways of neuronal activation. Substance-P-like immunoreactivity (SP-LI) and neurokinin-A-like immunoreactivity (NKA-LI) was determined by radioimmunoassay in the perfusates. A significantly increased outflow of both SP-LI and NKA-LI was observed during perfusion of the lung with high potassium concentration (60 mM), the C-fiber activator capsaicin (1 .mu.M), bradykinin (1 .mu.M), histamine (100 .mu.M), or the nicotinic agonist dimethylphenyl piperazinium (DMPP) (32 .mu.M). Release of both SP-LI and NKA-LI could also be achieved by electrical stimulation of vagal nerves. The percental increase varied from 80 to 1,000% depending on the kind of stimulus. The release of tachykinins by K+ or capsaicin was greatly reduced in calcium-free medium. Release by histamine was completely inhibited by 1 .mu.M mepyramine, and release by DMPP was abolished by 20 .mu.M hexamethonium. High performance liquid chromatography indicated that NKA-LI consisted of several cross-reacting substances, presumably other peptides of the tachykinin family. Among the isolated mammalian tachykinins, NKA was the most potent one to contract tracheal smooth muscle of guinea pigs in vitro, followed by neurokinin B and by SP. Both NKA and SP relaxed the guinea pig pulmonary artery with similar potency. It is concluded that activation of peripheral endings of airway C-fibers leads to peripheral release of multiple bioactive peptide peptides of the tachykinin family. These peptides may influence tracheobronchial and vascular smooth muscle tone.