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Neurokinin A-induced bronchial hyperresponsiveness to methacholine in Japanese monkeys
G Tamura1, K Sakai, Y Taniguchi
1First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
The present study was designed to investigate whether neurokinin A (NKA) and substance P (SP) increase bronchial responsiveness to methacholine (MCh). Before and 1, 2, 3 and 4 weeks after three Japanese monkeys had inhaled 10(-8) M NKA and 10(-8) M SP for 2 min, bronchial responsiveness to inhaled MCh was evaluated. Pulmonary flow resistance (R1) and dynamic lung compliance (Cdyn) were used as pulmonary function tests. Dose-response curves of R1 to inhaled MCh were shifted to the left 1 to 4 weeks after NKA treatment, compared with that obtained before treatment. However, SP treatment did not change the R1 dose-response curve. Thus, bronchial responsiveness to MCh was increased by inhalation of 10(-8) M NKA in Japanese monkeys.
Insights
Neurokinin A (NKA) inhalation increased bronchial responsiveness to methacholine (MCh) in Japanese monkeys. Substance P (SP) did not affect this response, suggesting NKA specifically enhances airway reactivity.
Area of Science:
- Respiratory Physiology
- Neuroendocrinology
- Pharmacology
Background:
- Neurokinin A (NKA) and Substance P (SP) are tachykinins involved in airway inflammation and bronchoconstriction.
- Their specific roles in modulating bronchial responsiveness to other stimuli remain incompletely understood.
Purpose of the Study:
- To investigate the effects of NKA and SP on bronchial responsiveness to methacholine (MCh).
- To determine if NKA or SP inhalation alters airway reactivity in a primate model.
Main Methods:
- Japanese monkeys were exposed to NKA (10(-8) M) or SP (10(-8) M) for 2 minutes.
- Bronchial responsiveness to inhaled MCh was assessed before and 1, 2, 3, and 4 weeks post-inhalation.
- Pulmonary function tests, including pulmonary flow resistance (R1) and dynamic lung compliance (Cdyn), were utilized.
Main Results:
- Inhalation of NKA led to a leftward shift in the MCh dose-response curve for R1, indicating increased bronchial responsiveness.
- This effect was observed from 1 to 4 weeks after NKA treatment.
- SP inhalation did not significantly alter the MCh dose-response curve for R1.
Conclusions:
- Neurokinin A, but not Substance P, significantly increases bronchial responsiveness to methacholine in Japanese monkeys.
- These findings suggest a specific role for NKA in modulating airway reactivity, potentially contributing to airway hyperresponsiveness in certain respiratory conditions.