Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo.
BACKGROUND
Administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We recently developed a guinea pig model for propranolol-induced bronchoconstriction (PIB). Neuropeptides which are released from C-fibre nerve endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation.


OBJECTIVE
The purpose of this study was to examine whether sensory neuropeptides are involved in the development of PIB after allergic reaction.


METHODS
Propranolol at a concentration of 10 mg/ml was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea pigs. The animals were treated intravenously with a NK1 and NK2 dual antagonist, FK224, in a dose of 1 or 10 mg/kg or vehicle or a selective NK1 antagonist, FK888, in a dose of 1 or 10 mg/kg or vehicle 10 min before or 15 min after antigen challenge.


RESULTS
Propranolol inhaled 20 min after antigen challenge caused bronchoconstriction. FK224 or FK888 administered 15 min after antigen challenge as well as 10 min before antigen challenge did not reduce the PIB.


CONCLUSIONS
We conclude that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of PIB after allergic reaction.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan.
Tsujiura
M
M
Myou
S
S
Ishiura
Y
Y
Matsuda
T
T
D000319:Adrenergic beta-Antagonists / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008297:Male; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011433:Propranolol / Q000633:toxicity*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D004151:Dipeptides; D007211:Indoles; D010456:Peptides, Cyclic; C075570:FK 224; C078949:FK 888; D013373:Substance P; D015288:Neurokinin A; D011433:Propranolol