Published ahead of print on October 11, 2004, doi:10.1164/rccm.200405-600OC Am. J. Respir. Crit. Care Med., Volume 171, Number 3, February 2005, 212-216 A more recent version of this article appeared on February 1, 2005
Submitted on May 10, 2004 A Novel Role for Tachykinin Neurokinin-3 Receptors in Regulation of Human Bronchial Ganglia NeuronsAllen C Myers1*,1 Department of Medicine, The John Hopkins University, Baltimore, MD, USA, 2 Department of Pharmacology, The University of Western Australia, Perth, Western Australia, Australia, 3 Respiratory and Inflammation Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, PA, USA * To whom correspondence should be addressed. E-mail: almy{at}jhmi.edu.
The neuropeptide tachykinins and their receptors have been implicated in the pathogenesis of lung disease, although the role of the tachykinin neurokinin-3 receptor has not been elucidated. Using confocal microscopy, we identified tachykinin neurokinin-3 receptors on human bronchial parasympathetic ganglion neurons. Electrophysiological recordings demonstrated that activation of sensory nerve fibers, either by antidromic stimulation or capsaicin, depolarized these neurons. This response was mimicked by exogenously applied tachykinin neurokinin-3 receptor-selective agonist, senktide analog, but not significantly by tachykinin neurokinin-1 or neurokinin-2 receptor-selective agonists. Responses to endogenous tachykinins or exogenous selective tachykinin neurokinin-3 receptor activation with senktide analog were inhibited by the selective tachykinin neurokinin-3 receptor antagonists, SB 223412 or SB 235375. We provide the first evidence that tachykinin neurokinin-3 receptors regulate human bronchial parasympathetic ganglion neurotransmission by activation of a peripheral reflex. This pathway may play a significant role in controlling bronchomotor tone and air flow to the lung. Key words: asthma, COPD, bronchoconstriction, airways, neurokinins157
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
