A novel role for tachykinin neurokinin-3 receptors in regulation of human bronchial Ganglia neurons.
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.
Department of Medicine, The Johns Hopkins University, Baltimore, MD, USA. amyers@jhmi.edu
Allen C
AC
Myers
Roy G
RG
Goldie
Douglas W P
DW
Hay
D000085:Acetates / Q000494:pharmacology; D000328:Adult; D001980:Bronchi / Q000294:innervation*; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D005726:Ganglia, Parasympathetic / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000085:Acetates; C444647:N-(alpha-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide; D010446:Peptide Fragments; D011804:Quinolines; D018042:Receptors, Neurokinin-3; C054724:senktide; C106716:SB 223412; D013373:Substance P; D002211:Capsaicin