Catecholaminergic microcircuitry controlling the output of airway-related vagal preganglionic neurons

Musa A. Haxhiu, Prabha Kc, Burim Neziri, Bryan K. Yamamoto, Donald G. Ferguson, V. John Massari

Research output: Contribution to journalArticle

28 Scopus citations


In this study, we have investigated the ultrastructure and function of the catecholaminergic circuitry modulating the output of airwayrelated vagal preganglionic neurons (AVPNs) in ferrets. Immunoelectron microscopy was employed to characterize the nature of catecholaminergic innervation of AVPN at the ultrastructural level. In addition, immunofluorescence was used to examine the expression of the α2A-adrenergic receptor (α2A-AR) on AVPNs, and norepinephrine release within the rostral nucleus ambiguous (rNA) was measured by using microdialysis. Physiological experiments were performed to determine the effects of stimulation of the noradrenergic locus coeruleus (LC) cell group on airway smooth muscle tone. The results showed that 1) catecholaminergic nerve endings terminate in the vicinity of identified AVPNs but very rarely form axosomatic or axodendritic synapses with the AVPNs that innervate the extrathoracic trachea; 2) AVPNs express the α2A-AR; 3) LC stimulation-induced norepinephrine release within the rNA region was associated with airway smooth muscle relaxation; and 4) blockade of α2A-AR on AVPNs diminished the inhibitory effects of LC stimulation on airway smooth muscle tone. It is concluded that a noradrenergic circuit originating within the LC is involved in the regulation of AVPN activity within the rNA, and stimulation of the LC dilates the airways by the release of norepinephrine and activation of α2A-AR expressed by AVPNs, mainly via volume transmission.

Original languageEnglish (US)
Pages (from-to)1999-2009
Number of pages11
JournalJournal of Applied Physiology
Issue number5
StatePublished - May 1 2003
Externally publishedYes


  • Locus coeruleus
  • Nucleus ambiguus; α-adrenergic receptors
  • Synaptic transmission
  • Volume transmission

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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