Hypersensitivity of pulmonary chemoreflex induced by poly-L-lysine: role of cationic charge.
This study was carried out to investigate the role of cationic charge in the hypersensitivity of pulmonary C-fibers induced by airway exposure to synthetic cationic protein poly-L-lysine (PLL) in anesthetized rats. Inhalation of PLL aerosol induced a distinctly irregular breathing pattern, and significantly enhanced the pulmonary chemoreflex responses to capsaicin. However, after the cationic charges were completely removed from PLL by succinylation, the succinylated PLL no longer produced any change in either the baseline breathing pattern or the reflex responses to capsaicin. In addition, the effects of PLL were also abolished after premixing it with a polyanion, poly-L-glutamic or poly-L-aspartic acid, before delivery. In sharp contrast, when delivered within 5 min after the PLL aerosol, these two polyanions were completely ineffective in reversing the effects of PLL. Electrophysiological recording of the afferent activity of single pulmonary C-fibers further supported our conclusion that the cationic charge carried by this protein is primarily responsible for generating the stimulatory and sensitizing effects of PLL on these afferents.
Department of Physiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, 40536-0298, USA.
Qihai
Q
Gu
Ruei-Lung
RL
Lin
Thomas C
TC
Vanaman
Lu-Yuan
LY
Lee
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology*; D002628:Chemoreceptor Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006967:Hypersensitivity / Q000209:etiology*; D008168:Lung / Q000187:drug effects*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects*; D011107:Polylysine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects; D013997:Time Factors
D002412:Cations; C060309:succinyl-polylysine; D011107:Polylysine; D002211:Capsaicin