Involvement of endogenous tachykinins in LTD4-induced airway responses.
Leukotriene D4-(LTD4) has been reported to cause tachykinin release from airway sensory nerves. However, the functional significance of endogenously released tachykinins in LTD4-mediated airway responses has not been fully clarified. The aim of this study was to investigate whether LTD4-induced airway responses are due, in part, to tachykinin release in guinea-pigs. Airway plasma exudation and bronchoconstriction were assessed by measuring extravasation of Evans blue dye and by mean pulmonary resistance (RL) in the presence of atropine (1 mg.kg-1 i.v.) and propranolol (1 mg.kg-1 i.v.), respectively. LTD4 (5 micrograms.mL-1 for 1 min) inhalation caused increase in plasma exudation and RL. Capsaicin pretreatment of animals to deplete sensory neuropeptides significantly inhibited LTD4-induced plasma exudation in the main bronchi, but not in the central (cIPA) and peripheral intrapulmonary airways (pIPA). Pretreatment with specific tachykinin neurokinin-1 (NK1)-receptor antagonists, FK 888 (10 mg.kg-1 i.v.) and CP 96345 (4 mg.kg-1 i.v.), also significantly reduced LTD4-induced plasma exudation in the main bronchi, and in the main bronchi and cIPA, respectively. However, these antagonists did not significantly affect the LTD4-induced increase in RL. In contrast, neurokinin-2 (NK2)-receptor antagonist, SR 48968 (0.3 mg.kg-1 i.v.), significantly inhibited the bronchoconstriction after LTD4-inhalation. These results suggest that leukotriene D4-induced bronchoconstriction and plasma exudation in guinea-pigs are, in part, due to tachykinin release from airway sensory nerves.
Ishikawa
J
J
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ichinose
M
M
Miura
M
M
Kageyama
N
N
Yamauchi
H
H
Tomaki
M
M
Sasaki
Y
Y
Shirato
K
K
D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D012137:Respiratory System / Q000187:drug effects; D015320:Tachykinins / Q000187:drug effects / Q000378:metabolism*
D002867:Chromones; D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D015320:Tachykinins; C078949:FK 888; D005070:Evans Blue; D017998:Leukotriene D4; D002211:Capsaicin; C047681:pranlukast