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A Novel Role for Tachykinin Neurokinin-3 Receptors in Regulation of Human Bronchial Ganglia Neurons

Department of Medicine, The Johns Hopkins University, Baltimore, Maryland; Department of Pharmacology, The University of Western Australia, Perth, Western Australia, Australia; and Respiratory and Inflammation Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania

Correspondence and requests for reprints should be addressed to Allen C. Myers, Ph.D., The Johns Hopkins Asthma and Allergy Center, 5501 Bayview Boulevard, 1A.62, Baltimore, MD 21224. E-mail: amyers{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. Electrophysiologic 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 analogue, 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 analogue 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: airways • asthma • bronchoconstriction • chronic obstructive pulmonary disease • neurokinins

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